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Ahmed, A. M. S. "Micellization of phenothiazines and their interaction with liposomes." Thesis, Cardiff University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372325.
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Drummond, Patricia Mary. "A comparative photostability study of four propyl piperzine-substituted phenothiazines." Thesis, Rhodes University, 1997. http://hdl.handle.net/10962/d1003234.
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Four structurally related phenothiazines available in South Africa in a variety of dosage forms and as fine chemicals were investigated to ascertain whether their structural differences in terms of the 2-chloro-/ trifluoromethyl-substituents on the phenothiazine nucleus and the methyl-/ ß-hydroxethyl groups on the piperazine ring accouning for the differences in pharmacological activity can be correlated with their photostability².The four propyl piperazine-substituted derivatives are ranked in the following decreasing order of neuroleptic activity: fluphenazine> trifluoperazine> perphenazine > rochlorperazine. In order to assess their photostability an HPLC method was developed and validated for linearity, accuracy and precision, selectivity, limit of detection and quantitation and ruggedness. Preliminary solution photostudies under controlled light conditions (UV, sunlight, fluorescent light) indicated that the rate of degradation followed first-order kinetics with perphenazine the most susceptible to.photodegradation under all light conditions studied. In vitro and in vivo metabolism yielding the 5-sulphoxide and its reported presence on decomposition of the phenothiazines25 led to the development of a synthetic procedure suitable for the sutphoxides of all four derivatives based on the method proposed by Owens et al. in order to provide standards for comparison in the photostudies⁷. Since ICH regulations require that impurities> 0.1 % are examined and identified⁷⁴ and semi-preparative isolation of photoproducts proved unsuccessful, LC-MS having been well documented for structural.elucidation⁷⁵ ⁷⁵ ⁷⁶ ⁷⁷ was used to characterize solution (UV, sunlight, fluorescent light) and preliminary solid (UV) photostudies. The chloroderivatives underwent dechlorination and sulphoxidation with subsequent photosubstitution in the case of prochlorperazine to yield the 2-hydroxy derivative and sulphoxidation of the dechloro-derivative of perphenazine. The sulphoxides of both trifluoperazine and fluphenazine were formed with further oxidation to the respective sulphones occurring. Preliminary solid state (UV) photostudies showed fluphenazine to be the least stable with 30.71 % degradation as opposed to 7.57% for prochlorperazine, 4.28% for perphenazine and 7.10% for trifluoperazine witn sulphoxidation observed to be. the major degradation pathway. Since in vitro metabolism of perazine derivatives is reported to occur via N-oxidation, N-demethylation, sulphoxidation and aromatic hydroxylation¹⁸ it does appear that there is some correlation between metabolic and photoproducts. However the fact that solution (UV) photostudies indicates trifluoperazine to be the most and perphenazine the least stable does not concur with the proposed order of pharmacological activity.
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Dunbar, Philip Gordon. "Approaches to the synthesis of pentacyclic dibenzazepines and phenothiazines." Diss., The University of Arizona, 1987. http://hdl.handle.net/10150/184295.
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Rigid analogues of the tricyclic antidepressant imipramine and the phenothiazine tranquilizer promazine were designed and their syntheses were attempted. Conformational rigidity was expected to reduce the side effects of these drugs by limiting their binding to multiple receptors. Ortho-directed metalation followed by acylation provided synthetic intermediates for the formation of the desired pentacyclic congeners. The known dilithiation of phenothiazine and iminodibenzyl and n-butyllithium, followed by acylation with dimethylformamide, gave carboxaldehydes at the 1 and 4 positions respectively. Ortho-lithiated nicotinamides were acylated by these aldehydes exclusively at the 4 position to provide the key intermediate alcohol amides. Difficulties in amide hydrolysis are discussed. Catalytic hydrogenation over palladium-on-carbon in refluxing acetic acid yielded carboxylic acids, apparently via the gamma-lactones formed in situ. The lactones could not be isolated easily due to instability to oxidation. Pentacyclic lactams were formed by dehydration, and borane was used to reduce the carbonyl function. Only the iminodibenzyl lactam was reduced, and problems encountered in subsequent pyridine ring reduction are discussed. Cis and trans ring fusion isomers were identified by ¹³C nmr. Attempted one-pot synthesis of this pentacycle and a regioisomer by double acylation of 4,5-dilithioiminodibenzyl with 2,3-pyridinedicarboxylic anhydride, and 3,4-pyridinedicarboxylic anhydride failed. Mechanistic considerations are discussed regarding regiochemistry and reactivity of the nitrogen and carbon anions involved. Ortho-lithiation of 3-bromopyridine to form 3-pyridyne in the presence of the preformed N-lithioiminodibenzyl-4-carboxaldehyde was unsuccessful in providing a pentacyclic benzonaphthyridinobenzazepine. The resulting 2- and 4-lithiated 3-bromopyridines were trapped by the aldehyde instead. Both hydroxymethylbromopyridines were identified by their proton coupling patterns in the pyridine ring. These compounds are discussed as potential precursors to pentacyclic benzazepinopyridobenzazepines. Several other attempts at forming benzonaphthyridinobenzazepines and naphthyridinophenothiazines were unsuccessful. Intermediates were obtained by carbon acylation of the dilithiated iminodibenzyl and phenothiazine with arecoline esters, arecaidine, and pyridine-3-carboxaldehyde. Dibenzylic alcohol reduction is discussed, as is its labile oxidation. None of the resulting pyridylmethyl heterocycles could be cyclized.
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Ferrara, Daro 1961. "DETECTION OF PHENOTHIAZINES USING COATED WIRE ION-SELECTIVE ELECTRODES." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/276493.
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Omoruyi, Sylvester Ifeanyi. "Investigating the anti-cancer activity of novel phenothiazines in glioblastoma." University of the Western Cape, 2018. http://hdl.handle.net/11394/6329.
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Philosophiae Doctor - PhDGlioblastoma multiforme (GBM) remains the most malignant of all primary adult brain tumours. It is a highly invasive and vascularized neoplasm with limited treatment options and very low survival rate. GBM tumours are heterogeneous in nature with cellular hierarchy and at the apex of this hierarchy are the glioblastoma stem cells, known to promote tumourigenesis and resistance to chemotherapeutic agents and tumour recurrence. Currently, the standard care for GBM involves surgical resection, radiation, and chemotherapy treatment with temozolomide. Unfortunately, median survival after treatment is still daunting and tumour relapse is very frequent. Indeed, patients with recurrent glioblastoma have less than a year survival. To address this, novel therapies need to be developed with the early introduction of promising agents into clinical trials and subsequent approval for use. Importantly, for these novel therapies to be approved for GBM, they need to be safe, effective as well as being able to penetrate the blood-brain barrier (BBB). Due to the high cost and process time for the development of new drugs, existing approved drugs are currently being repurposed for new indications and this is gaining significance in clinical pharmacology as it allows rapid delivery of useful drugs from bench to bedside. Drugs of the antipsychotic class are well known to cross the BBB due to their neuroleptic action. To this end, the aim of this study was to identify and characterize the anti-cancer activities of novel phenothiazine-derivatives belonging to the antipsychotic class of drugs in glioblastoma. To achieve this, several novel phenothiazine-derivatives were initially screened for possible anti-cancer activity in the U87 and U251 malignant GBM cells. Two lead compounds, DS00326 and DS00329, were identified and their anti-cancer activities were determined in U87 and U251 cells as well as in primary patient-derived xenograft (PDX) glioblastoma cultures. DS00326 and DS00329 significantly inhibited glioblastoma cell viability, with minimal effects observed in the non-cancerous FG0 fibroblasts. The IC50 values of DS00326 and DS00329 for U251, U87 and PDX cells ranged from 1.61 to 12.53μM. Flow cytometry analyses showed that DS00326 and DS00329 treatment led to an increase in the G1 population of cells. Additionally, DS00326 and DS00329 induced double-strand DNA breaks, which lead to activation of the canonical DNA damage response pathway. Furthermore, DS00326 and DS00329 induced apoptosis as shown by morphological markers, flow cytometry with annexin V-FITC/propidium iodide staining, as well as western blotting with an antibody to detect levels of cleaved PARP. Interestingly, treatment with DS00326 and DS00329 also induced autophagy as evident by the increase of acidic vesicular organelles in cells following staining with acridine orange as well as an increase in levels of the autophagy marker LC3-II. Autophagy was seen as a pro-death pathway in the U87 and U251 cells as inhibition of autophagy led to a reversal of cytotoxicity and consequently increased cell survival. Moreover, it was demonstrated that DS00326 and DS00329 inhibited the PI3/Akt pathway while modulating the mitogen-activated protein kinases p38, ERK1/2 and JNK signalling pathways. Importantly DS00326 and DS00329 displayed anti-cancer stem cell activities by the inhibition of neurosphere formation and regulation of stem cell markers SOX2 and GFAP in PDX cells. Together, the findings from this study suggest that DS00326 and DS00329 may be effective in the treatment of glioblastoma and provide a strong rationale for further clinical studies exploiting phenothiazines and their derivatives as treatments for glioblastoma.
2021-09-01
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GUEVARA, ELMER AUGUSTO CUEVA. "FOTODEGRADATION OF PHENOTHIAZINES AND THEIR STRUCTURAL EFFECTS ON NA(+)K(+) - ATPASE: A FLUORESCENCE STUDY." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2010. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=15952@1.
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CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOClorpromazina (CPZ), flufenazina (FPZ) e trifluperazina (TFP) são derivados de fenotiazinas que, sob irradiação UV, geram fotoprodutos. Observouse que CPZ desenvolve três fotoprodutos fluorescentes em diferentes condições. A promazina (PZ) se forma da fotólise de CPZ pela quebra da ligação com o cloro. A saída do cloro é um dos principais caminhos para a formação de outros fotoprodutos, sendo também um requisito para formação de dímeros e trímeros de CPZ. O segundo produto fluorescente é a espécie sulfóxida, que se desenvolve em presença de oxigênio somente em meio ácido e tem pico de fluorescência em (aproximadamente) 370 nm. A terceira espécie, com pico triplo de emissão e máximo em 352 nm, se desenvolve predominantemente em ausência de oxigênio. Observou-se que as taxas de formação dos fotoprodutos fluorescentes são maiores em meio ácido. FPZ e TFP apresentaram o mesmo fotoproduto fluorescente (emissão (aproximadamente) 410 nm), espécie que se desenvolve em presença de O2 com as mesmas características da espécie sulfóxida. A fluorescência do fotoproduto da TFP foi testada como sensor de radiação UV e para detecção de pequenas quantidades de oxigênio. Estudando as interações com membranas contendo a enzima Na(+), K(+)-ATPase, mostrou-se que as fenotiazinas alteram a estrutura lipídica da membrana, já que aumentam a anisotropia de fluorescência da sonda de membrana DPH. Os resultados da interação das fenotiazinas com resíduos de triptofano da proteína mostraram supressão de fluorescência de mais da metade dos triptofanos, sem transferência de energia. A estrutura local do sítio de ATP na proteína Na(+), K(+)-ATPase, marcado com a sonda fluorescente FITC, não foi afetada pela interação com as fenotiazinas, sugerindo que a localização do sítio de ligação das fenotiazinas com a enzima fica longe do sítio de ATP.
Chlorpromazine (CPZ), fluphenazine (FPZ) and trifluoperazine (TFP) are phenothiazine derivatives, which generate photoproducts under UV irradiation. We observed that CPZ develops three fluorescent fotoproducts under different conditions. Promazine (PZ) that forms from the CPZ photolysis. The chlorine loss is one of the main pathways for photoproduct formation and it seems to be a requirement for development of CPZ dimers or trimers. The sulfoxide species with fluorescence peak at (aprroxomately) 370 nm develops in the presence of oxygen only in acid conditions. Another fluorescent species with structured emission and maximum at 352 nm develops primarily in the absence of oxygen. It was observed that the development rates of all fluorescent photoproduct are greater under acidic conditions. FPZ and TFP presented the same fluorescent photoproduct (emission (approximately) 410 nm), which develops in the presence of O2 with the same characteristics as the sulfoxide derivative. The fluorescence of the TFP photoproduct was tested as a UV sensor and a sensor for detection of small amounts of oxygen. Studying the interactions with Na+, K+-ATPase enriched membranes, phenothiazines were shown to modify the membrane lipid structure since they increased the fluorescence anisotropy of the membrane probe DPH. The results of phenothiazine interaction with tryptophan residues of the enzyme showed fluorescence quenching of (approximately) 50% of the tryptophan residues, without energy transfer. The local structure of the Na(+), K(+)-ATPase ATP binding site, labeled with FITC, was not affected by the interaction with the phenothiazines, suggesting that the phenothiazine sites are far from the ATP binding site.
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Fenart, Naud Dominique. "La photosensibilite au neuriplege : a propos de 8 observations, photo-allergie croisee entre la chlorproethazine et les autres phenothiazines." Lille 2, 1988. http://www.theses.fr/1988LIL2M103.
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Semenya, Manare Molahlegi Dorothy. "Non-Neuroleptic Antitubercular and Anticancer Therapeutics through Rational Drug Remodelling of Phenothiazines and Related Antipsychotics." Thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33391.
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In light of shrinking pharmaceutical drug pipelines and drug resistance, innovative drug discovery strategies are of imperative need. Drug repurposing and related strategies such as drug rescue and drug remodelling have garnered significant research interest. Various clinically approved non-antibiotics including phenothiazines hold promise as novel classes of therapeutics in other indications. However, in addition to inherent neuroleptic properties, phenothiazines and related antipsychotics elicit adverse side effects at clinically relevant doses thus precluding their extensive clinical application. Herein, it was postulated that the selectivity of phenothiazines and related drugs for nonneuroleptic indications could be enhanced through rationalized structural remodelling. Phenothiazine and related neuroleptics are known to obey a lipophilic chromophore/basic side chain paradigm. Deviation from this paradigm is expected to decrease potential for neuroleptic effects. Therefore, the remodelling strategies involved introduction of novel functionalities that are dissimilar to native phenothiazine structures. Prior to chemical synthesis, drug metabolism and pharmacokinetic related properties were predicted in silico to assess drug-likeness of the new chemical entities derived from phenothiazines and related antipsychotics. The in silico profiling also included prediction of blood/brain partition coefficients and CNS activity to determine their likelihood of exhibiting neuroleptic effects. The new chemical entities were then evaluated against drug-susceptible Mycobacterium tuberculosis-H37Rv. Furthermore, a selected series was screened for binding to dopamine and serotonin receptors to corroborate in silico CNS activity predictions. Moreover, pharmacokinetic studies were conducted with the selected series to determine in vitro microsomal stability, kinetic solubility and in vivo toxicity profiles. Another objective of this study was to evaluate the new chemical entities for their potential as anticancer agents. The key findings herein demonstrated that it is possible to abolish neuroleptic effects through rationalized structural manipulation and still retain bio-activities of interest. Several new chemical entities including N-alkylsulfonates (DS0031, DS0032, DS0034, DS0035, DS00366) and nitrobenzenesulfonamides (DS00325, DS00326, DS00329) of phenothiazines, displayed notable antitubercular (GAST/Fe MIC90 range: 9.9-125 µM; 7H9 MIC range 12.5- 25 µg/mL) and anticancer (IC50 range 4.51-12.43 µM) activities in comparison to native phenothiazine drugs. Furthermore, in vitro and in vivo preclinical evaluation revealed favourable pharmacokinetic profiles. Overall, this study presents novel subclasses of phenothiazines that hold promise for further development as non-neuroleptic agents in either tuberculosis or cancer treatment regimens.
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Abouamer, Karima Massaud. "Application of natural dyes in textile industry and the treatment of dye solutions using electrolytic techniques." Thesis, Brunel University, 2008. http://bura.brunel.ac.uk/handle/2438/5088.
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Anodic oxidation of a commercial dye, methylene blue (MB), from aqueous solutions using an electrochemical cell is reported. Data are provided on the effects of eight different types of supporting electrolytes, concentration of electrolytes, initial dye concentration, current and electrolytic time on the percentage removal of methylene blue. Anodic oxidation was found to be effective in achieving the removal of methylene blue from aqueous solutions. The optimised electrolytic conditions, for the removal of methylene blue (MB), were applied to the removal of azure A (AA), azure B (AB), azure C (AC), toluidine blue 0 (TBO), new methylene blue (NMB), dimethyl methylene blue (DMMB), thionine (TH), methylene green (MG), methyl violet (MV), Nile blue (NB), neutral red (NR), acridine orange (AO) and resorufin (RS) from aqueous solutions containing sodium chloride. Results indicated that between 84 to 100% of each dye of phenothiazine was removed during 60 minutes of electrolysis. The percentage removals for the phenothiazine dyes followed the following decreasing order: (MG ≈ MV) > (DMMB ≈ AA) > (AB ≈ AC ≈ NMB) > TBO > TH. However, the azine, acridine and oxazine dyes showed between 98 to 99% colour removal and the following decreasing order: NB ≈ NR > AO ≈ RS. Strongly electron withdrawing substituents such as nitro group or carbonyl group increases the degradation of the phenothiazine chromophore, whereas the electron donating groups such as amino and alkyl amino groups decrease the degradation. Anodic oxidation studies were extended to the destruction of eight permitted food colours, with azo and triarylmethane chromophore, from aqueous solution containing either sodium chloride or sodium sulphate as a supporting electrolyte. Again, sodium chloride was found to be the best supporting electrolyte and between 97 to 100% colour removal was achieved after 60 minutes of electrolysis. The percentage removal for the single azo based colourants followed the following increasing order: carmoisine > sunset yellow FCF > amaranth > ponceau 411 > tartrazine. However, the binary and ternary mixtures of food colour showed the following increasing order: blue > green > yellow food colours. The extractions and applications of 54 different types of natural dyes (53 from plants and one from animal origin) are evaluated using simple techniques. The extracted natural dyes were applied in dyeing three types of textile fabrics viz: a) paj silk, b) brushed cotton twill and c) crystallized shimmering satin. The effects of two eco-friendly mordants (alum and iron) on the dyeing process were compared with the dyeing process without mordants. The colour fastness to wash and light (both natural and artificial sun light) of these natural dyes were also assessed. The results showed that out of the 54 dyestuffs studied, 32 plants are potentially able to produce marketable natural dyes. These dyes produced good colour and met minimal performance standards for colour fastness to light and washing. The addition of mordants generally increased the fastness properties. Silk gave the best performance of dyeing uptake and stability. Cotton gave the poorest fastness properties. The overall results showed that, considering molecular associations, the fastness properties were of the order: anthraquinones and tannins> indigoid > flavones> flavonols > flavanols> carotenoids> anthocyanins. Anodic oxidation studies were extended to the destruction of ten natural dyes from aqueous solutions containing either sodium chloride or sodium sulphate as a supporting electrolyte. Anodic oxidation was effective in achieving the removal of green tea (35%), spinach (69%), Langdale yellow and turmeric (95%), carmine, saffron, henna (97%), beetroot, karkade and sumac (98%). However, TOC measurements and the UV analyses indicated that some organic intermediate compounds were formed in the presence of sodium chloride.
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LAASSIS, BELKACEM. "Etude de la fluorescence photoinduite d'une serie de phenothiazines en solution aqueuse et en presence de cyclodextrines - applications analytiques et pharmaceutiques." Paris 7, 1997. http://www.theses.fr/1997PA077047.
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Un groupe de phenothiazines a ete quantifie par application des methodes analytiques basees sur la fluorescence. Les mesures directes de la fluorescence native de ces composes n'ont donne que des performances analytiques mediocres avec des limites de detection de l'ordre de 10 a 110 ng/ml, mais leur photooxydation sous l'effet d'irradiation uv provoque une augmentation importante du signal de fluorescence, ce qui permet de developper une methode fluorimetrique photoinduite (pif) sensible, dans les conditions optimales de solvant (eau), ph et de temps d'irradiation. Les phenothiazines ont ete analysees sur une gamme de concentration de deux a trois puissances de dix avec des limites de detection comprises entre 3 et 70 ng/ml. La combinaison de la methode pif avec le systeme d'injection en flux (fia), pif-fia a permis d'ameliorer sensiblement le temps d'analyse et les performances analytiques ; les limites de detection etaient comprises entre 13 et 98 ng/ml, environ 100 echantillons pouvait etre analyses par heure. Les methodes pif en solution stationnaire et pif-fia ont montre leur fiabilite dans la determination des phenothiazines dans des echantillons biologiques (urines) et pharmaceutiques (medicaments). L'ajout de faibles concentrations de cyclodextrines a des solutions aqueuses tamponnees de phenothiazines, suivi d'irradiation uv, provoque une exaltation importante du signal de fluorescence photoinduite, ainsi que de faibles deplacements des pics d'excitation et d'emission (methode pif-cd). L'existence d'un complexe d'inclusion de stoechiometrie 1:1 entre les phenothiazines et les cyclodextrines a pu etre etabli. Les constantes de formation des complexes d'inclusion etaient comprises entre 90 et 3600 m#-#1 selon le compose. La presence des cyclodextrines a ameliore considerablement les performances analytiques, avec des limites de detection comprises entre 0. 03 et 30 ng/ml. Les spectres pif derives d'ordre un ont ete utilises pour analyser quantitativement des melanges binaires artificiels d'aminophenothiazines de differentes compositions sans separation prealable.
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Figueiredo, Eduardo Costa de. "Emprego de polimeros de impressão molecular (MIP) na extração e pre-concentração de analitos organicos em amostras biologicas seguido de determinação espectrofotometrica." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248589.
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Orientador: Marco Aurelio Zezzi ArrudaTese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica
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Resumo: Essa Tese de Doutorado teve como objetivo promover a associação entre polímeros de impressão molecular (MIP) e espectrofotometria, sendo a seletividade conseguida pela ligação específica dos analitos com os sítios de reconhecimento molecular impresso no MIP. No capítulo 1 foi sintetizado e caracterizado um MIP seletivo a catecol, sendo o mesmo empregado na extração de catecol em amostras de guaraná (Paullinia cupana) e mate (Ilex paraguariensis), seguido de determinação espectrofotométrica (reação não específica de redução de Mn(VII) para Mn(II) pelo catecol). Obteve-se um limite de quantificação, um desvio padrão relativo (20 mmol L, n=10) e uma freqüência analítica de 2,7 mmol L, <5% e 15h, respectivamente. A exatidão foi comprovada por comparação dos resultados obtidos pelo método proposto e por HPLC. No Capítulo 2 um MIP foi empregado na extração de nicotina em amostras de urina de fumantes, seguido da quantificação por espectrofotometria (reação de redução do Mn(VII) a Mn(VI)). O limite de quantificação e a freqüência analítica foram de 1,1 mmol L e 11 h, respectivamente. As precisões intra-ensaio (10, 13 e 4%) e inter-ensaio (12, 10 e 5%) foram obtidas empregando-se padrões de 3, 10 e 30 mmol L, respectivamente e a exatidão foi comprovada por meio da técnica de HPLC. No capítulo 3 foi reportado o emprego do MIP na extração de fármacos fenotiazínicos (clorpromazina e perfenazina) em amostras de urina de pacientes. Após a extração, os fármacos foram eluidos e separados, à baixa pressão e alta velocidade, em uma coluna de C18 com tamanho de partícula entre 35 e 50 mm. Os limites de quantificação foram de 5 mmol L, para ambos os fármacos, e a exatidão foi comprovada por adição de analitos e pela técnica de HPLC
Abstract: The objective of this Thesis was the association between molecularly imprinted polymers and spectrophotometry, with the selectivity obtained through specific binding between analytes and imprinted binding sites of the polymer. In the Chapter 1, a selective MIP for catechol was synthesized, characterized, and employed for the extraction of catechol from guarana (Paullinia cupana) and mate (Ilex paraguariensis) samples, followed by indirect spectophotometric determination of catecol by reduction of Mn(VII) for Mn(II). A limit of quantification, a relative standard deviation (20 mmol L, n = 10) and an analytical frequency of 2.7 mmol L, <5% and 15h, were obtained, respectively. Accuracy was validated using HPLC. In the Chapter 2, a MIP for nicotine was used for its extraction in urine samples of smokers, followed by its indirect quantification by spectrophotometry (reduction of Mn(VII) to Mn(VI) by nicotine). The limit of quantification and analytic frequency were of 1.1 mmol L and 11 h, respectively. Intra (10, 13 and 4%) and inter-day (12, 10 and 5%) precisions were obtained using 3, 10 and 30 mmol L nicotine standard solutions, respectively, and accuracy was validated through HPLC. Finally, in the Chapter 3, a MIP was employed for phenothiazinics (chlorpromazine and perphenazine) extraction in urine samples. Soon after, the drugs were eluted and separated using a low pressure and high-speed system, comprising a C18 column with particle size between 35 and 50 mm. The quantification limits were 5 mmol L for chlorpromazine and perphenazine, and the accuracy was validated using HPLC
Doutorado
Quimica Analitica
Doutor em Ciências
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Santos, Vivian Matsukura dos. "Caracterização de mecanismos bioquímicos e moleculares da morte celular induzida por fenotiazinas em células leucêmicas humanas." reponame:Repositório Institucional da UFABC, 2014.
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Orientador: Prof. Dr. Tiago RodriguesTese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biossistemas, 2014.
Fenotiazinas (FTZ) sao farmacos psicotropicos utilizados no tratamento de esquizofrenia. Foram relatadas diversas propriedades biologicas interessantes das FTZ, dentre elas, efeitos na prevencao do cancer, atividade pro-apoptotica e reversao da resistencia a multiplas a drogas (MDR) por inibicao da glicoproteina P (Pgp). Neste trabalho, nos avaliamos os efeitos citotoxicos das FTZ sobre celulas leucemicas humanas que expressam ou nao o fenotipo MDR Lucena-1 e K562, respectivamente e os mecanismos de morte celular envolvidos. Nossos resultados demonstraram que as FTZ apresentaram atividade citotoxica nas linhagens K562 e Lucena-1 de maneira concentracao-dependente. Nos observamos que apesar da efetividade das FTZ ser praticamente a mesma nas celulas K562 e Lucena-1 os mecanismos envolvidos no processo de morte celular sao bastante distintos. A morte celular induzida por FTZ em celulas K562 parece ocorrer por apoptose e e disparada por aumento subito de Ca2+ citosolico, geracao de especies reativas de oxigenio (EROs) acompanhada da oxidacao de grupos tiolicos e dissipacao do ¿¢¿µ. Em paralelo foi observado que a morte celular induzida por FTZ em celulas K562 envolve a participacao de permeabilizacao de membrana lisossomal (PML) e da autofagia. Em contrapartida, a morte celular induzida pelas FTZ em celulas Lucena-1 parece ocorrer por necrose e nao ha participacao de calcio. Entretanto a geracao de EROs e a oxidacao de grupos tiolicos parecem ter participacao importante no processo, uma vez que o agente redutor, DTT preveniu completamente a morte celular induzida pelas FTZ em celulas Lucena-1. Nos sugerimos que as FTZ utilizam a necrose como mecanismo alternativo de morte de celulas Lucena-1, uma vez que este modelo celular apresenta alteracoes que bloqueiam a maquinaria apoptotica. Estes dados sugerem um potencial farmacologico destes compostos na quimioterapia antitumoral, como possivel estrategia em caso de resistencia a quimioterapia classica.
Phenothiazines (PTZ) are psychotropic drugs used in schizophrenia treatment. It were reported several interesting biological properties of PTZ,among then, effects in cancer prevention, pro-apoptotic activity and reversal of multidrug-resistant (MDR) by P-glycoprotein inhibition. We evaluate in this study the PTZ effects over the human leukemic viability that express or not the phenotype MDR Lucena-1 and K562, respectively and the cell death mechanisms involved. Our results demonstrated that PTZ showed cytotoxic activity in K562 and Lucena-1 cell lines in a concentrationdependent way. We could observe that besides the PTZ effectiveness being practically the same in the K562 and Lucena-1 the mechanisms involved in the cell death process are very distinct. Cell death induced by PTZ in K562 cells seems to occurs by apoptosis and is triggered by a sudden cytosolic Ca2+increase, ROS generation together with thiol groups oxidation and ÄØ dissipation. In parallel it was noticed that the PTZ-induced cell death in K562 cells involves the participation of lysosomal membrane permeabilization (LMP) and autophagy. In contrast, cell death induced by PTZ in Lucena-1 cells seems to occur by necrosis and there is no calcium participation. Therefore the ROS generation and the thiol groups oxidation seems to have important participation in the process, once that a reduction agent, the DTT completely prevented the cell death induced by PTZ in Lucena-1 cell. We suggest that PTZ used the necrosis as an alternative mechanism for Lucena-1 cell death, once that this cell model shows alterations that block the apoptotic machinery. These data suggest a pharmacological potential of this compounds in antitumor chemotherapy and possible strategy in case of classic chemotherapy resistance.
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Gomes, Júnior Rafael Araújo. "Efeitos de compostos naturais, sintéticos e da fototerapia antifúngica sobre Candida tropicalis resistente ao fluconazol." Centro de Pesquisas Gonçalo Moniz, 2014. https://www.arca.fiocruz.br/handle/icict/9954.
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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
A candidíase é uma infecção oportunista provocada por diversas espécies de fungos do gênero Candida, frequentemente encontrados integrando a microbiota, da superfície cutânea, no trato gastrointestinal e cavidades mucosas do ser humano desde o seu nascimento. A incidência das infecções fúngicas sistêmicas têm aumentado consideravelmente nas últimas décadas em função do grande número de pacientes com SIDA, a grande quantidade de transplantes e condições crônicas como o câncer, a terapia prolongada com imunossupressores e o uso de agentes corticosteroides. Além disso, a exposição prolongada aos antifúngicos azólicos promove a seleção de patógenos resistentes. No presente estudo avaliou-se a atividade antifúngica do complexo Rutênio-pirocatecol (RPC) frente a um isolado clinico de Candida tropicalis resistente ao fluconazol. A metodologia empregada para os testes de susceptibilidade foi de acordo com o documento M27-A3 do National Committee for Clinical Laboratory Standards (NCCLS, 2008). Esplenócitos de camundongos Balb/c foram obtidos de forma asséptica para avaliar a citotoxicidade do composto para células de mamíferos. O estresse oxidativo promovido pelo composto foi avaliado através da reação ao ácido tiobarbitúrico (TBARS) e ensaios de fluorescência com a sonda diclorodihidrofluoresceína diacetato (DCFH2DA). O Calcofluor White foi empregado para avaliar a integridade da parede celular. A análise ultraestrutural foi realizada através da microscopia eletrônica de varredura e transmissão. Os resultados encontrados para os testes de atividade antifúngica foram analisados através do teste estatístico ANOVA e pós-teste Dunnett. Os resultados encontrados para os testes de atividade antifúngica do RPC mostraram uma Concentração Inibitória de 50% (IC50) de 20,3 μM, enquanto em esplesnócitos a concentração efetiva de 50% foi de 325 μM mostrando um índice de seletividade igual a 16. O referido composto também mostrou um elevado efeito pró-oxidante quando avaliamos os níveis de estresse oxidativo através da TBARS e por meio da sonda DCFH2DA. Quando as leveduras foram tratadas por 24 h com o referido composto, observamos na microscopia de varredura o desenvolvimento de pseudo-hifas com 9 μM, a formação de fissuras em sua parede e uma forte agregação das células com 18 μM, além disso, encontramos uma intensa redução na quantidade de células e muito debris celular com 38 μM. Na microscopia de transmissão observamos estruturas vesiculares no espaço periplasmático associado a grânulos eletrondensos, os quais também foram vistos associados a parede celular, quando tratadas por 3h com 40 μM. No tratamento por 24h com 60 μM observamos a referida estrutura granular eletrondensa no citoplasma envolta por membrana, uma grande quantidade destas estruturas no espaço citoplasmático e associado a parede da célula, além disso, também observamos trechos de membrana associado a estas estruturas no espaço extracelular. Em conclusão, a atividade antifúngica e o índice de seletividade do RPC contra uma cepa resistente é consideravelmente interessante devido as suas possibilidades de aplicações na descoberta de novos antifúngicos
Candidiasis is an opportunistic infection caused by several species of fungi of the genus Candida, often found is the microbiota, on the skin, gastrointestinal tract and mucous cavities of the human beings birth. The incidence of systemic fungal infections have increased considerably in recent decades due to the large number of AIDS patients, the large number of transplants and chronic conditions such as cancer, prolonged therapy promotes the selection of resistant pathogen with immunosuppressant and corticosteroid agents. Also prolonged exposure azole antifungals to make them strong candidates for patients resistance. In the present study we evaluated the antifungal activity of Ruthenium-pyrocatechol complex (RPC) against a clinical isolate of Candida tropicalis resistant to fluconazole. The methodology for susceptibility testing was in accordance with the M27-A3 document of there National Committee for Clinical Laboratory Standards (NCCLS, 2008). Splenocytes from Balb/c mice were obtained aseptically to evaluate the cytotoxicity of the compound to mammalian cells. Oxidative stress caused by the compound was assessed by reaction to thiobarbituric acid (TBARS) and fluorescence assays with the probe diclorodihidrofluoresceína diacetate (DCFH2DA). The Calcofluor White was used to evaluate the integrity of the cell wall. The ultrastructural analysis was performed by scanning and transmission electron microscopy. The results for the antifungal activity tests were analyzed using ANOVA and pos-test Dunnett test statistic. The results for the tests of antifungal activity of the RPC showed a 50% inhibitory concentration (IC50) of 20.3 μM while in splenocytes the 50% effective concentration was 325 μM showing a selectivity index of 16. The compound also showed that a high pro-oxidant effect when evaluated levels of oxidative stress by TBARS and through DCFH2DA staining. When yeast cells were treated for 24 h with this probe, in scanning microscopy we observed the development of pseudohyphae 9 μM, the formation of cracks on their fungal walls and in these cell aggregation with 18 μM furthermore found a remarkable reduction in the number of cells, and cell debris with 38 μM. In transmission microscopy vesicular structures observed in the periplasmic space associated with electrondense granules, which were also seen associated with the cell wall, when there cells were treated for 3 h with 40 μM. In the treatment for 24h with 60 μM observed that the grain structure in the clusters in periplasmic, a large amount of these structures in the cytoplasmic space and associated with the cell wall, moreover, we also observe membrane portions associated with these structures in the extracellular space. In conclusion, the antifungal activity and the selectivity index RPC against a resistant strain is pretty interesting because of its possible applications in the discovery of new antifungal agents.
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Dutra, Danilo Antonio Milbradt. "AVALIAÇÃO DO FOTOSSENSIBILIZADOR AZUL DE METILENO EM DIFERENTES FORMULAÇÕES PARA USO EM TERAPIA FOTODINÂMICA." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/6112.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThe present study evaluated different formulations of methylene blue (MB) with the aim to improve the antimicrobial effect of photodynamic therapy. Photophysical and photochemical properties and antimicrobial effect of the MB dissolved in different formulations: water (MB/water); 20% ethyl alcohol (MB/ethanol); 0,1% chitosan solution (MB/chitosan); and in mixture of water, ethanol and chitosan (50:20:30 v:v) (MB/new formulation), was evaluated. Molecular aggregation of MB, evaluated by monomer-to-dimer ratio, was dependent on MB concentration and the solvents used. The MB/water and MB/chitosan formulations showed higher aggregation than MB/ethanol and MB/new formulation. In substrate oxidation models (Uric acid and N-acetyl-l-tryptofanamide) the formulation MB/new formulation showed the greatest ability to form singlet oxygen and greater photo-oxidation kinetics. In vitro biofilms of Enterococcus faecalis (Gram positive) and Escherichia coli (Gram negative) was used to evaluated the antimicrobial effect of MB different formulations. No difference was observed when biofilms was treated with MB/water (Light +) and MB/water (Light -). The MB/new formulation group (Light +) showed significant decrease to MB/water (Light -) for both microorganisms. The MB formulation dissolved in water, ethanol and chitosan showed promising photochemical, photophysical, and antimicrobial results. Our results demonstrated that different solvents can enhanced the antimicrobial effect of photodynamic therapy.
Diferentes formulações de azul de metileno (AM) com objetivo de potencializar o efeito antimicrobiano da terapia fotodinâmica foram avaliadas. Propriedades fotofísicas, fotoquímicas e antimicrobianas do MB dissolvido em: água (MB/água); álcool etílico 20% (MB/etanol); quitosana 0,1% em solução de ácido acético 1%/água (30:70 v:v) (MB/quitosana); e sistema água, etanol e quitosana (50:20:30 v:v) (MB/nova formulação), foram avaliadas. Agregação molecular do AM, mensurada pela razão entre a proporção de monômeros e dímeros, foi dependente da concentração do AM e dos solventes. Formulações AM/água e AM/quitosana apresentaram maior agregação molecular do que AM/etanol e AM/nova formulação. Utilizando os modelos de oxidação de substrato (Ácido Úrico e NATA), AM/nova formulação apresentou maior capacidade para formação de oxigênio singleto e maior cinética de foto-oxidação. O efeito antimicrobiano foi avaliado sobre biofilmes in vitro de Enterococcus faecalis (Gram positiva) e Escherichia coli (Gram negativa). Nenhuma diferença estatística foi observada quando biofilmes foram tratados com AM/água com foto-ativação (L+) ou sem foto-ativação (L-). O grupo tratado com AM/nova formulação (L+) apresentou redução significativa em relação ao controle (AM/água L-) para ambos os micro-organimos. A utilização da formulação de AM em água, etanol e quitosana apresentou resultados fotoquímicos e antimicrobianos promissores, demonstrando que diferentes solventes podem potencializar o efeito antimicrobiano da terapia fotodinâmica.
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Xiao, Shaorong. "The electrochemistry of phenothiazine derivatives." Thesis, University of Central Lancashire, 2000. http://clok.uclan.ac.uk/20876/.
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Methylene blue derivatives (MBDs) such as methylene blue (MB -), 1-methyl methylene blue (1MMB) and 1,9-dimethyl-methylene blue (DMMB) have potential use as drugs within photodynamic therapy (PDT). Knowing the redox properties of MBDs will help in understanding the way in which MBDs interact with a range of biological systems. In this work, the electrochemical behaviour of MBDs at various solution pHs have been studied for the first time on gold microdisc electrodes using steady state and non-steady state cyclic voltammetric methods. Steady-state studies The reduction of MBDs is an ECE(CC) process where the C steps are protonation reactions. The number (m) of W participating in the overall electrode process increases from 1 to 2 or 3 with decreasing pH although the profile is different among MBDs. The half-wave potential (E 112) of each methylene blue derivative (MBD) shifts to more negative potential with increasing pH values. The E 112 of MBD at the same pH shifts to more cathodic potentials with an increasing number of -CH 3 substituent, indicating that the thermodynamic facility of MB, lMMB and DMMB reduction decreases with increasing the number of -CH3 substituents. The reduction products of MBDs depend strongly on pH, sweep rate, and sweep potential limit, as well as number of -CH 3 substituents. Non-steady state studies The redox behaviour of MBDs under non-steady-state conditions is complicated. Their common characteristics are that (i) the initial reduction of MBD is a diffusion controlled process; (ii) the onset potentials for MBD reduction shift to more negative potentials with increasing pH and number of CH 3 substituents; (iii) the facility of observation of the charge transfer complex increases with increasing pH; (vi) the charge transfer complex can be further reduced at more cathodic potentials; and (v) the amounts of charge transfer complex and leuco form depend on sweep rate and sweep potential window. They also have some differences among the electrochemical behaviour of the three drugs, such as, some anodic and cathodic processes may occur in one of MBDs, and some may not. Possible mechanisms for the electroreduction of MBDs are suggested and discussed in the light of the effect of pH and potential sweep rate on the reaction products.
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Antunes, Edith Martins. "Stability of prochlorperazine in solution and in the solid-state." Thesis, Rhodes University, 2000. http://hdl.handle.net/10962/d1016399.
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Prochlorperazine, a member of the piperazine subclass of phenothiazines, widely used as an anti-emetic, is susceptible to oxidation to sulfoxides. These are main metabolites and degradants of all phenothiazines which are found to be inactive at the dopamine receptors. Prochlorperazine causes photosensitivity effects in patients attributed to dechlorination at C2 with the release of HCI (Huang and Sands, 1967; Nejmeh and Pilpel, 1978; Moore and Tamat, 1980). The aim of this study is to investigate the thermal and photostability of prochlorperazine edisylate and mesylate salts in the solid state and in solution. Prochlorperazine is available as a fine chemical and in a variety of dosage forms, including injectables and tablets. According to ICH guidelines, any degradants greater than 0.1 % are required to be isolated and identified. In order to assess the photostability of the two salts, an HPLC method was developed and validated for linearity, accuracy and precision, selectivity, limit of detection, quantitation and ruggedness. Sulfoxides were synthesised for use as standards in the rate studies according to the well-known hydrogen peroxide method (Owens et al., 1989). The rate of prochlorperazine degradation in solution under various light sources (254 nm UV light, diffuse light and sunlight) was studied. The light sources used abovF were quantified using potassium ferrioxalate as a chemical actinometer). The photodegradation rate was found to be greater in ampoules sealed under nitrogen than air, but the thermal degradation was faster in ampoules sealed with air than those purged with nitrogen. Amber ampoules retarded the rate of degradation under all photolytic conditions. This is a vital consideration for the packaging and storage of prochlorperazine in injectables. Degradation was found to occur mainly by first-order kinetics and the degradation rate decreased in the following order: sunlight » UV light 254 nm > fluorescent I diffuse light. Solid state samples, however, were found to be relatively stable to the various light / heat conditions over a 6 month period when compared to prochlorperazine solutions, but still considerably unstable. Thus both storage and packaging is a vital consideration for prochlorperazine injectables. The thermal behaviour of mixtures of prochlorperazine with standard excipients, was assessed for potential interactions, using differential scanning calorimetry. For most of the excipients (magnesium stearate, stearic acid, Explotab®, AC-Di-Sol®, Encompress® and Ludipress®, lactose and Starch 1500®) disappearance or broadening of the melting endotherm of the drug indicated interactions. Lubritab®, however, was the only 'inert' excipient tested. Liquid chromatography - mass spectrometry (LC-MS) was used to determine the nature of the degradation products. The major degradation pathways included dechlorination and demethylation of the parent drug, as well as sulfoxidation and Noxidation. Prochlorperazine underwent dechlorination and sulfoxidation with subsequent photosubstitution to yield the 2-hydroxy derivative. The solid state photostudies showed the formation of dealkylated, oxidised and hydroxylated products, sulfoxides and dimers. Since N-demethylation, N-oxidation, sulfoxidation and aromatic hydroxylation are reported to occur in the in vitro metabolism of perazine derivatives, it does appear that there is some relationship between metabolites and photoproducts (Breyer, 1974). This study has been successful in providing understanding of the photolytic and thermal degradation pathways of prochlorperazine.
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Jones, T. "Structure disposition relationships amongst phenothiazine drugs." Thesis, Cardiff University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379191.
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Junqueira, Helena Couto. "Síntese e estudo das propriedades fotoinduzidas de derivados fenotiazínicos em sistemas biomiméticos." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-18122008-105257/.
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Neste trabalho são apresentados estudos do efeito de interfaces nas propriedades fotofísicas e fotoquímicas do azul de metileno (AM) e de derivados fenotiazínicos com o intuito de avaliar o potencial destes compostos como fotossensibilizadores (FS) em terapia fotodinâmica. As propriedades físico-químicas do AM foram estudadas em soluções de SOS e observou-se que a presença do AM em solução altera o equilíbrio entre as micelas de SOS, diminuindo o valor da concentração micelar crítica de 7mmolL-1 para 70µmoIL-1. A presença das micelas em solução também interfere nas propriedades do AM. Em baixas concentrações de SOS há formação de dímeros de AM, constatados pelo aumento da absorbância em 580nm e diminuição da emissão de fluorescência. A caracterização das espécies transientes mostrou a existência de moléculas de azul de metileno no estado triplete (3AM) e de oxigênio singlete em soluções com altas concentrações de SOS e a formação de espécies radicalares do AM em baixas concentrações do tensoativo. Esta observação sugere que o mecanismo fotoquímico do AM é dependente da sua concentração local próxima de interfaces carregadas. As interações do AM e de alguns de seus derivados fenotiazínicos (tionina, azure A e azure B) com vesículas e com células HeLa foram estudadas e em ambos os casos observou-se que as moléculas com estruturas assimétricas são incorporadas em maior extensão. Em estudos de fototoxicidade, os compostos assimétricos apresentaram maior nível de morte celular do que o verificado para os compostos simétricos. Entretanto, ao se considerar a incorporação em células, os compostos simétricos se mostraram mais eficientes por molécula. Foi desenvolvido um método para determinação do 10gP dos fotossensibilizadores (FS) por voltametria com microeletrodos que se mostrou reprodutível. Novos FSs assimétricos derivados do Azure A com duas caudas hidrofóbicas de 4, 6 e 8 carbonos (AzC4, AzC6 e AzC8) foram sintetizados. Esses novos compostos possuem eficiências de fluorescência semelhantes ao AM. O composto AzC4 apresenta eficiência de geração de oxigênio singlete bem próxima à do AM (0,56), enquanto os outros dois compostos têm uma eficiência de geração de oxigênio singlete cerca de duas vezes menor. Este comportamento se deve ao fato dos FSs com cadeias carbônicas maiores interagirem mais fortemente entre si, apresentando maior grau de agregação. Os compostos sintetizados apresentam maior incorporação em vesículas que os compostos anteriormente estudados, indicando que a assimetria da molécula favorece a incorporação, assim como, o comprimento da cadeia hidrofóbica. Resultados de incorporação em células HeLa, mostraram que o composto AzC4 interage mais facilmente com a membrana celulare apresenta maior nível de morte celular devido à sua maior incorporação.The effect of interfaces on photophysical and photochemical properties of methylene blue (MB) and its derivatives was studied in this work, aiming to emploit their potencial as photosensitizers (PS) in photodynamic therapy.The presence of MB in SDS solutions affect the micelle equilibrium decreasing the apparent critical micelle concentration of SDS from 7mmolL-1 to 70µmoIL-1. The properties of MB were also affected. At low SDS concentrations the formation of MB dimers was detected by the increase in the absorption in 580 nm and decrease of fluorescence emission. The characterization of transient species of MB showed the existence of MB molecules in the triplet state and emission of singlete oxygen at large SDS concentration and the formation of MB radicals in small surfactant concentration. These observations suggest that the photochemical mechanism of MB depends on its local concentration close to charged interfaces.The interactions of MB as well as other phenotiazine derivatives with synthetic vesicles and HeLa cells were studied. In both cases, the PS with asymmetrical structure presented higher degrees of incorporation. Studies of phototoxicity showed that the PS with asymmetrical structures present higher degree of cell death than the symmetrical compounds. However, if one consider the degree of incorporation the symmetrical compounds are more efficient per molecule. A method to determinate logP by voltammetry with microelectrodes was developed, showing good repeatability. New asymmetric photosensitizers derived from Azure A with two hydrophobic chains of 4, 6 or 8 carbons (AZC4, AZC6 e AzC8) were synthesized in order to study structure/activity relationship. These new compounds presented similar fluorescence efficiency to MB. The oxygen singlet generation efficiency of AZC4 is similar to MB, while the efficiency of the other PSs was twice smaller. This behavior was explained in terms PS aggregation, due to their longer hydrophobic chains. The synthesized PSs presented larger degree of incorporation than the commercial PSs, showing the role of asymmetry and hydrophobicity in incorporation yields. Incorporation in HeLa cells showed that AZC4 interacts more strongly with cells than the other synthesized PSs due to the rigidity of plasmatic membrane. Under the same illumination conditions, AzC4 was the PS that presented higher degree of cell death as a result of its larger incorporation in cells.
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Barbosa, Leandro Ramos Souza. "Estudo de sistemas de relevância biológica por espalhamento de raios X a baixos ângulos." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-20032009-101046/.
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Neste trabalho, utilizamos a técnica de espalhamento de raios-X a baixos Ângulos (SAXS) para estudar a influência de dois derivados fenotiazínicos na estrutura de sistemas micelares, assim como suas propriedades de auto-associação, além de investigar a influência da variação de pH e de concentração nas interações entre proteínas em solução. Para tanto, utilizamos dois fármacos fenotiazínicos, (Trifluoperazina, TFP e a Clorpromazina, CPZ), em presença de L--fosfatidilcolina (LPC), um surfactante zwiteriônico (30 mM), a pH 4.0 e 7.0. Os resultados de SAXS indicam que a micela de LPC, em ausência de fenotiazina, pode ser representada por uma micela com forma elipsoidal (com razão axial 1.6 0.1). No entanto, em presença de TFP e de CPZ a forma da micela se altera, passando para um cilindro (com razão axial 2.5 0.1). Este efeito é acompanhado por uma diminuição do raio parafínico da micela (22.5 0.3 Å), em ausência de fármaco, para 20.0 0.5 em presença de 10 mM de fármaco. Em paralelo, realizamos medidas de EPR (Ressonância Paramagnética eletrônica) destes sistemas. Combinando os resultados de SAXS e de EPR, propusemos um sítio para a localização destes compostos nas micelas de LPC, que seria na interface polar/apolar da mesma. Em um segundo momento, utilizamos as técnicas de SAXS e de EPR para investigar as características estruturais dos agregados formados por TFP e CPZ (a 20 e 60 mM, a pH 4.0 e 7.0). As curvas de SAXS são compatíveis com o espalhamento de agregados pequenos com diferentes geometrias: elipsoidal, cilíndrico e tipo-paralelepípedo. Devido à resolução da técnica, dentro do intervalo de vetores de espalhamento utilizada (até cerca de 0.3 Å-1), não é possível determinar, de forma absoluta, a correta geometria dos agregados, ou seja, todas as geometrias citadas acima ajustam de forma satisfatória as curvas de SAXS. As análises dessas curvas também não excluem a possibilidade de que estes fármacos mantenham-se como nano-cristais em solução (compostos por cerca de 10 celas unitárias, empilhadas na direção-z), seguindo sua estrutura cristalográfica. Medidas de EPR indicam que os auto-agregados a pH 4.0 possuem características semelhantes às micelas, mas a pH 6.5 este efeito não foi evidenciado, uma vez que ocorre uma forte interação entre a sonda e os agregados. Este fato indica que os agregados, a pH 6.5, têm um maior empacotamento, em comparação aos sistemas a pH 4.0. Por fim, utilizamos a Albumina de Soro Bovina (BSA, a 10 50 mg/ml), em diferentes pHs (2.0 9.0), para investigar os efeitos de concentração e de pH nos potenciais de interação das macromoléculas em solução. O fator de forma da proteína foi obtido através da estrutura cristalográfica da HSA (Human Serum Albumine, proteína humana homóloga a BSA), enquanto que as interações proteína-proteína foram calculadas através da relação de fechamento RPA (Random Phase Approximation). Nossos dados indicam que a BSA mantém sua estrutura terciária inalterada de pH 4.0 a 9.0, independente de sua concentração. No entanto, a pH 2.0 a proteína sofre um processo de desenovelamento, indicado pelo aumento da dimensão máxima da mesma. Nossos dados dão suporte para concluir que as interações entre as proteínas, a 10 mg/ml, são praticamente desprezíveis, exceto para os sistemas compostos a pH 2.0 (onde a proteína está desenovelada) e a pH 4.0 (onde evidenciamos a presença de interferência atrativa entre as proteínas). Entretanto, a medida em que aumentamos a concentração proteica, uma função de interferência do tipo repulsiva aparece na curvas de SAXS (para os sistemas de pH 4.0 a 9.0). Além disso, no sistema composto por BSA, pH 5.4 e 50 mg/ml, evidenciamos a existência de monômeros e dímeros em solução, provavelmente devido a proximidade do ponto isoelétrico da proteína (entre 4.8 5.6). Este efeito não foi evidenciado para os outros pHs, nesta mesma concentração. A pH 2.0 (25 e 50 mg/ml) evidenciamos uma compactação da proteína, sendo que sua forma é diferente da forma nativa da BSA. Nestas condições, é possível que a proteína tenha alcançado um estado molten globule, como evidenciado em outros trabalhos. Acreditamos que os efeitos de volume excluído são de grande importância para a estabilidade da proteína in vivo.In this work we study, mainly by means of small angle X-ray scattering (SAXS), the influence of two phenothiazine derivatives on biomimetic systems as well as the self-assembly features. At the same time, the conformational stability of proteins in the presence of denaturant agents (pH and concentration) was evaluated. First of all, the phenothiazine compounds trifluoperazine (TFP) and chlorpromazine (CPZ) with micelles of the zwitterionic surfactant L--lysophosphatidylcholine (LPC), at pHs 4.0 and 7.0, are reported. The SAXS results demonstrate that, upon addition of both phenothiazines, the LPC micelle of prolate ellipsoidal shape changes into a cylindrically shaped micelle, increasing its axial ratio from 1.6 0.1 (in the absence of drug) to 2.5 0.1 (for 5 and 10 mM of phenothiazine). Such an effect is accompanied by a shrinking of the paraffinic shortest semiaxis from 22.5 0.3 to 20.0 0.5 Å. Besides, EPR (Electronic Paramagnetic Resonance) evidenced a bigger motion immobilization of the nitroxe probe, in the presence of phenothiazines. Our results provide evidence that the positively charged phenothiazine molecule must be accommodated near the hydrophobic/hydrophilic inner micellar interface. Furthermore, SAXS and EPR experiments were carried out to investigate the structure of the self-aggregates of CPZ and TFP, in aqueous solution. SAXS studies (drug solutions of 20 and 60 mM, at pH 4.0 and 7.0) evidenced that several different particle form factors with a homogeneous electron density distribution, in respect to the water environment, could reproduce the scattering curves. Due to the limitation of scattering intensity in the q range above 0.15 Å-1, precise determination of the aggregate shape was not possible and all of the tested models for ellipsoids, cylinders, or parallelepipeds fitted the experimental data equally well. The SAXS data allows inferring, however, that CPZ molecules might self-assemble in a basis set of an orthorhombic cell, remaining as nanocrystallites in solution. Such nanocrystals are composed of a small number of unit cells (up to 10, in c-direction), with CPZ aggregation numbers of 60-80. EPR spectra of 5- and 16-doxyl stearic acids bound to the aggregates were also performed, indicating a micelle-like aggregate at pH 4.0, and a significant motional restriction of the nitroxide was observed at pH 6.5. This implies that the aggregate is densely packed at this pH and that the nitroxide is tightly bound to it producing a strongly immobilized EPR spectrum. Finally, the effect of concentration and pH on the protein-protein interactions of BSA (Bovine Serum Albumin, from 10 up to 50 mg/ml) was evaluated by SAXS. Our results give support to infer that BSA keeps its native shape (similar to the Human Serum Albumin, HSA, crystallographic structure) unaltered at middle-acid (pH 4.0) up to basic pHs (9.0). At pH 2.0, however, BSA undergoes an unfolding process, indicated by a non globular shape. The protein-protein interactions were analysed into the Random Phase Approximation. The results show that at smaller amounts of BSA (10 mg/ml) the interference effects are not significative over the SAXS curve for pH 5.4 up to 9.0. At pH 4.0 and 10 mg/ml, however, an attractive potential takes place over the SAXS curves, that becomes repulsive with increasing BSA concentration. Besides, at pH 5.4 and 50 mg/ml, we evidenced a dimer-monomer co-existence in the solution. At pH 2.0 and 25 and 50 mg/ml, BSA undergoes to a compact conformation. Probably, BSA is in a molten globule state. Our results give also support to infer that probably, the exclude volume effect plays an important role on the protein stability in vivo.
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Pasini, Marcela Mozzaquatro. "AVALIAÇÃO DE DIFERENTES FORMULAÇÕES DE AZUL DE METILENO NA TERAPIA FOTODINÂMICA EM DOENÇA PERIODONTAL INDUZIDA EM RATOS." Universidade Federal de Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/6138.
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Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorThis study aimed to evaluate the histological effect of different formulations of Methylene Blue (MB) used in antimicrobial Photodynamic Therapy (aPDT) as adjuvant to conventional treatment, on gingival collagen fibers in the treatment of periodontal disease induced in rats. In this study were used 120 male rats (Rattus Novergicus, Wistar lineage). The periodontitis was induced by placing a ligature on right mandibular first molar in 105 rats. After 7 days, they were removed and the animals were randomized in 5 groups: NC negative control; PC positive control (no treatment); SRP - scaling and root planning (SRP) and periodontal pocket irrigation with saline solution; aPDT SRP + aPDT (with MB 0,01% dissolved in water + laser); aPDT/ethanol SRP + aPDT (with MB 0,01% dissolved in solvents containing ethanol 20% + laser). The NC animals received neither periodontitis induction nor treatment. Five animals of NC and PC and ten animals of SRP, aPDT and aPDT/ethanol are euthanized 7, 15 and 30 days after treatment. Gingival samples were collected to the quantification of collagen fibers and descriptive analysis of collagen type I and III proportion and organization. Data were analyzed with ANOVA and multilevel Poisson regression analysis. The animals of NC, PC, SRP, aPDT and aPDT/ethanol showed percentage of collagen fibers area of 67,99%, 45,71%, 58,39%, 71,70% and 72,37%, respectively, but no statistical difference was seen in aPDT and aPDT/ethanol; the collagen fibers area was higher at 30 days (71,37%) than at 7 days (60,25%) and at 15 days (63,12%) after treatment, showing statistical difference only at 30 days (ANOVA). Considering multivariate Poisson regression analysis, aPDT and aPDT/ethanol showed 6% higher rate of collagen fibers organization when compared to NC (p<0,05); this organization increased 5% at 15 days after treatment and 19% at 30 days when compared to 7 days (p<0,05). The action of different formulations of MB was similar concerning the quantity and organization of gingival collagen fibers, presenting higher collagen type I quantity, parallel and dense alignment at 30 days after treatment. According to the experimental model used in this study, the ethanol presence in MB formulation doesn t interfere on collagen fibers quantity and quality of collagen fibers in periodontal wound healing. This study suggests the aPDT could be a promising alternative to periodontal disease treatment as adjuvant to conventional treatment.
Este estudo objetivou avaliar histologicamente o efeito de diferentes formulações de Azul de Metileno (AM), na Terapia Fotodinâmica antimicrobiana (TFDa), como adjuvante ao tratamento periodontal convencional, sobre as fibras colágenas do tecido gengival no tratamento da doença periodontal induzida em ratos. Neste estudo, foram utilizados 120 ratos machos (Rattus Novergicus, linhagem Wistar). A periodontite foi induzida pela colocação de ligaduras no molar inferior direito em 105 ratos. Decorridos 7 dias, as ligaduras foram removidas e os animais foram randomizados em 5 grupos: CN - controle negativo; CP - controle positivo (sem tratamento); RAR - raspagem e alisamento radicular (RAR) e irrigação da bolsa periodontal com solução salina; TFDa - RAR + TFDa (com AM a 0,01% dissolvido em água + laser); e TFDa/etanol - RAR + TFDa (com AM a 0,01% dissolvido em solventes contendo etanol a 20% + laser). Os animais do CN não foram submetidos à indução de doença ou tratamento. Cinco animais de CN e CP e dez animais de RAR, TFDa e TFDa/etanol foram eutanasiados em 7, 15 e 30 dias após os tratamentos. Amostras de tecido gengival foram coletadas para quantificação das fibras colágenas e análise descritiva da proporção e organização dos tipos I e III de colágeno. Dados foram analisados com ANOVA e análise multinível de Regressão de Poisson. Os animais de CN, CP, RAR, TFDa e TFDa/etanol mostraram percentual de área das fibras colágenas de 67,99%, 45,71%, 58,39%, 71,70% e 72,37%, respectivamente, porém nenhuma diferença estatística foi observada entre TFDa e TFDa/etanol; a área das fibras colágenas foi maior aos 30 dias (71,37%) do que aos 7 dias (60,25%) e aos 15 dias (63,12%) após o tratamento, apresentando diferença estatística somente aos 30 dias (ANOVA). Considerando a análise multivariada da Regressão de Poisson, TFDa e TFDa/etanol apresentaram uma taxa 6% maior de organização das fibras colágenas quando comparados ao CN (p<0,05); tal organização aumentou 5% aos 15 dias após o tratamento e 19% aos 30 dias, quando comparados aos 7 dias (p<0,05). A ação das diferentes formulações do AM foi semelhante no que diz respeito à quantidade e organização das fibras colágenas do tecido gengival, apresentando maior quantidade de colágeno tipo I, com alinhamento paralelo e denso aos 30 dias após o tratamento. De acordo com o modelo experimental utilizado neste estudo, a presença do etanol na formulação do AM não interfere na quantidade e na qualidade das fibras colágenas frente ao processo de cicatrização periodontal. Este estudo sugere que a TFDa pode ser uma alternativa promissora para o tratamento da doença periodontal como adjuvante ao tratamento convencional.
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Meary, Alexandre. "Schizophrenie et cancer du poumon." Paris 6, 2001. http://www.theses.fr/2001PA062055.
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Wilson, Beth. "Syntheses and DNA Interactions of Acridine and Phenothiazine Based Photosensitizers." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/8.
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Photosensitizing molecules and/or metal complexes that interact with DNA via intercalation and groove binding have potential applications as molecular structural probes, as footprinting reagents and in photodynamic therapeutics. To this regard, small molecules that bind to DNA and the energetics involved in these interactions, acridine-based therapeutics, photosensitization, photodynamic therapy, phenothiazine-mediated photosensitization, DNA photocleavage reaction mechanisms and photosensitizing metal complexes are introduced in Chapter I. Next, in Chapter II, the synthesis of a photonuclease consisting of a 3,6-acridinediamine chromophore attached to four metal-coordinating imidazole rings is described. The DNA photocleavage yields, emission quantum yields, and thermal denaturation studies by this acridine-imadazole conjugate in the presence of 16 metal salts are also reported. In Chapter III is the synthesis of a bisacridine covalently tethered to a copper(II)-binding pyridine linker. Additionally, DNA photocleavage studies as well as DNA binding affinity and binding mode(s) of this bisacridine incorporating the copper(II)-binding pyridine linker are examined. The syntheses, characterization, DNA photocleavage studies, DNA thermal denaturation, and viscometric measurements of three new phenothiazinium photosensitizers are described in Chapters IV and V. Collectively, markedly enhanced DNA photocleavage yields are observed in the presence of metals (Chapters II-III) or in comparison to a parent molecule, Chapters II and IV. DNA melting isotherms show higher levels of duplex stabilization with the acridines, specifically in the presence of several metals (Chapter II-III) as well as with the phenothiazine-based ligands (Chapters IV-V). Moreover, different DNA binding modes were observed depending on metal complexation (Chapter III) and nucleic acid structure (Chapter IV). Finally, Chapter VI describes a small project implemented as a National Science Foundation pedagogical laboratory exercise in which a non-invasive procedure for DNA isolation from human cheek cells was utilized with the polymerase chain reaction to amplify alleles encoding a single nucleotide polymorphism involved in normal human color vision.
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Silenzi, Ilaria. "Synthesis, characterization and conformational studies of bis-phenothiazine-aryl-boranes." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/19201/.
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This thesis project presents a work based on the study of a particular class of amino-boranes, called bis-phenothiazine-aryl-boranes. The peculiarity of these compounds is the N-B-N chemical moiety and their complex conformational behaviour, due to the combination of steric hindrance and conjugation of the B-N bond. Our work is focused on two main products with different symmetry: bis-phenothiazine-2-methylnaphthyl-borane (2b) and bis-phenothiazine-anthracenyl-borane (2c). We firstly focused our attention on an effective way of synthesis, by optimizing both reaction conditions and purification. The products and co-products of interest were then characterized with NMR, mass spectroscopy and X-Ray diffraction on single crystals. The products were eventually analysed through conformational studies, by experimental techniques, such as dynamic NMR and EXSY, and by a theorical approach with DFT calculations.
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Shirdel, Javid. "Photo-physical characterization of flavin-pyrene-phenothiazine molecular photonic complexes." [S.l.] : [s.n.], 2007. http://deposit.ddb.de/cgi-bin/dokserv?idn=985128062.
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Takorabet, Lila. "Immuno-régulation de la fonction thyroïdienne par une phenothiazine, l'alimemazine." Paris 5, 1996. http://www.theses.fr/1996PA05CD05.
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La glande thyroïde est le siège de deux maladies auto-immunes : la thyroïdite de Hashimoto et la maladie de Basedow. Ces deux pathologies qui sont opposées tant par leur caractéristiques immunologiques qu'endocrinologiques sont d'origine multifactorielles : c'est de l'interaction de plusieurs facteurs de risque que naît la maladie. Cependant, la capacité d'expression par les cellules épithéliales thyroïdiennes (CET) des molécules de classe II du complexe majeur d'histocompatibilité (CMH) au cours de pathologie auto-immune thyroïdienne, transforme ces cellules en cellule présentatrice d'antigène (APC) professionnelles. Dans le premier volet de notre travail, nous avons étudié le rôle physiologique des anti-corps monoclaux (Acm) anti-récepteur de la TSH (R-TSH) sur la prolifération des CET. Tous les Acm anti-R-TSH induisent une prolifération des CET, cependant, variable d'un Acm à l'autre. Nous avaons également décrit un nouveau rôle pathogénique des Acm anti-R-TSH. En effet, nous avons montré clairement le rôle de ces Acm anti-R-TSH dans la modulation des molécules de classe II du CMH des thyrocytes, impliquées dans la reconnaissance immunologique. A ce jour, aucun Acm anti-R-TSH n'a été décrit qui stimule l'expression des molécules de classe du CMH. Si de tels Ac existent dans la patologie de Basedow, ils pourraient jouer un rôle aggravant dans la maladie en développant même en l'absence de l'IFN-y, la capacité des CET à présenter ses propres auto-antigènes (AAg) aux lymphocytes T autoréactifs. Dans la seconde partie, nous avons évalué le rôle d'une phénothiazine, l'alimémazine couramment utilisée en pédiatrie, sur l'expression des Ag de classe II CMH dans les CET murines et humaines, sachant que le gavage des rats par cette drogue induit des désordres thyroïdiens : infiltration lymphocytaire de la glande thyroïde et diminution du taux des hormones thyroïdiennes. Nous montrons que l'alimémazine utilisée à des concentrations physiologiques induit l'expression ectopique des molécules de classe II du CMH, augmente l'expression des Ag thyroïdiens (thyroglobuline (Tg) et le R-TSH) et des molécules d'adhésion (ICAM-1 et B7) à la surface des CET. En plus, une réponse allogénique et syngénique spécifique de la Tg murine a été observée en présence des CET traitées par l'alimémazine. L'ensemble de ces résultats suggère que l'alimémazine en induisant l'expression des Ag de classe II du CMH, des AAg thyroïdiens à la surface des CET et en favorisant le contact entre ces cellules et les lymphocytes, pourrait jouer un rôle dans l'induction et la perpétuation des désordres thyroïdiens auto-immuns.
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Collini, Melissa A. "Synthesis and Studies of AzaBODIPY Derived Donor-Acceptor Systems for Light Induced Charge Separation." Thesis, University of North Texas, 2018. https://digital.library.unt.edu/ark:/67531/metadc1404570/.
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The efficiency and mechanism of electron- and energy transfer events occurring in both in natural and synthetic donor-acceptor systems depend on their distance, relative orientation, and the nature of the surrounding media. Fundamental knowledge gained from model studies is key in building efficient energy harvesting and optoelectronic devices. Faster charge separation and slower charge recombination in donor-acceptor systems is often sought out. In our continued effort to build donor-acceptor systems using near-IR sensitizers, in the present study, we report ground and excited state charge transfer in newly synthesized, directly linked, tetrads featuring bisdonor (donor = phenothiazine and ferrocene), BF2-chelated azadipyrromethane (azaBODIPY) and C60 entities. The tetrads synthesized using multi-step synthetic procedure revealed strong charge transfer interactions in the ground state involving the donor and azaBODIPY entities. The near-IR emitting azaBODIPY acted as a photosensitizing electron acceptor along with fullerene while the phenothiazine and ferrocene entities acted as electron donors. The triads (bisdonor-azaBODIPY) and tetrads revealed ultrafast photoinduced charge separation leading to D•+-azaBODIPY•–-C60 and D•+-azaBODIPY-C60•– (D = phenothiazine or ferrocene) charge separated states from the femtosecond transient absorption spectral studies in both polar and nonpolar solvent media. The charge separated states populated the triplet excited state of azaBODIPY prior returning to the ground state.
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Fadiran, E. O. "Assay of phenothiazine sulphoxides by and temperature effects in second derivative spectrofluorimetry." Thesis, University of Strathclyde, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371950.
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Hart, Aaron S. "Substitution Effects of Phenothiazine and Porphyrin Dyes in Dye-sensitized Solar Cells." Thesis, University of North Texas, 2013. https://digital.library.unt.edu/ark:/67531/metadc407837/.
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The details of dye sensitized solar cells was explained and phenothiazine and porphyrin based dyes were synthesized for use in DSSCs. DSSCs offer a unique and cost effective method of renewable energy. DSSCs are characterized through various tests, with the overall efficiency, η, bearing the greatest importance. Incident photon to current conversion efficiency, or IPCE, is also another important characterization of DSSCs. Effect of positioning of the cyanoacrylic acid anchoring group on ring periphery of phenothiazine dye on the performance of dye sensitized solar cells (DSSCs) is reported. The performances of the cells are found to be prominent for solar cells made out of Type-1 dyes compared to Type-2 dyes. This trend has been rationalized based on spectral, electrochemical, computational and electrochemical impedance spectroscopy results. Free-base and zinc porphyrins bearing a carboxyl anchoring group at the para, meta, or ortho positions of one of the meso-phenyl rings were synthesized for DSSCs. Photoelectrochemical studies were performed after immobilization of porphyrins onto nanocrystalline TiO2. The performance of DSSCs with the porphyrin anchoring at the para or meta position were found to greatly exceed those in the ortho position. Additionally, zinc porphyrin derivatives outperformed the free-base porphyrin analogs, including better dye regeneration efficiency for the zinc porphyrin derivatives and for the meta and para derivatives through electrochemical impedance spectroscopy studies. The overall structure-performance trends observed for the present porphyrin DSSCs have been rationalized based on spectral, electrochemical, electrochemical impedance spectroscopy and transient spectroscopy results.
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潘多海 and Duohai Pan. "Nanosecond time-resolved resonance Raman and ab initio studies of triplet states and radical cations of halobiphenyls and the radicalcations of phenothiazine, promazine, and chloropromazine." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31240860.
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Pan, Duohai. "Nanosecond time-resolved resonance Raman and ab initio studies of triplet states and radical cations of halobiphenyls and the radical cations of phenothiazine, promazine, and chloropromazine /." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22237665.
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Golriz, Seyed Ahmad Ali [Verfasser]. "Phenothiazine based polymers for energy and data storage application / Seyed Ahmad Ali Golriz." Mainz : Universitätsbibliothek Mainz, 2013. http://d-nb.info/1034293931/34.
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Khelwati, Hilla [Verfasser]. "Synthese und Charakterisierung neuartiger Phenothiazine zur Darstellung von redoxaktiven mesoporösen Organokieselgelen / Hilla Khelwati." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2020. http://d-nb.info/1214439586/34.
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Peters, Jennifer Margaret 1956. "Synthesis and monoamine uptake inhibiting properties of perisubstituted tricyclic compounds." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/291828.
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The synthesis of 1-methyl-promazine, 4-hydroxymethyl-iminodibenzyl, and 4-bromo-5-trimethylsilyl-iminodibenzyl via dilithiation and ¹H-NMR's are described. Molecular modeling was done for the latter compound. The heat of dissociation was 30.6 kcal/mole for the lowest energy conformer. Rotational energies were examined for three bonds. The IC₅₀ values for inhibition of neurotransmitter uptake by rat brain synaptosomes were determined for a series of 1-substituted promazines, and 4-substituted imipramines. 1-Substituted promazines were fair inhibitors of serotonin uptake with an average IC₅₀ of 2000 nm. Their potency for inhibiting norepinephrine uptake was difficult to assess due to poor assay reproducibility, and the average IC₅₀ was estimated at 200 to 1700 nm. Serotonin, but not norepinephrine, uptake inhibition was increased with additional ring substitution at C(2) with a trifluoromethyl group. The 4-substituted imipramines were equal or slightly decreased in potency to unsubstituted imipramine for uptake inhibition of both neurotransmitters. IC₅₀'s were also reported for imipramine and desipramine.
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Ronzani, Filippo. "Réactions d’oxydation photosensibilisée : espèces transitoires réactives et mécanismes aux interfaces." Thesis, Pau, 2013. http://www.theses.fr/2013PAUU3020/document.
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L'objectif principal du travail effectué au cours de cette thèse était de développer, caractériser et analyser des matériaux originaux pour des réactions d'oxydation photosensibilisée. Une attention particulière a été accordée à la détermination des propriétés photophysiques des sensibilisateurs (PSs) et à l'effet induit par l'immobilisation sur un support inerte (silice). Les espèces réactives formées lors de l'irradiation ont été identifiées et analysées. La production d'oxygène singulet a été suivie par deux méthodes complémentaires. Les sensibilisateurs supportés ont été employés, sous la forme de monolithes ou de poudres, pour la photo-oxydation du diméthyl sulfure à l'interface gaz-solide et de l’-terpinène à l'interface liquide-solide. L'oxygène singulet est la principale espèce réactive de l’oxygène formée par les PSs sélectionnés; néanmoins, les produits de réaction ont été analysés afin de mettre en évidence d’autres mécanismesThe main aim of the work carried out during this PhD project was to develop, characterize and analyze original materials for photosensitized oxidation reactions. Particular attention was paid to the determination of the photophysical properties of the selected photosensitizers (PSs) and the effect induced by the immobilization on an inert support (silica). The reactive species formed upon irradiation were identified and analyzed. Singlet oxygen production was monitored by two complementary methods. The solid-supported sensitizers were employed, in the form of either monoliths or powders, for the photooxidation of dimethyl sulfide at the gas-solid interface and of -terpinene at the liquid-solid interface. Singlet oxygen was the main reactive oxygen species formed by the selected PSs; nonetheless, the reaction products were analyzed and other possible mechanistic scenarios investigated
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Lamprianidis, Panagiotis. "Photoredox catalysis with 10-phenyl-10H- phenothiazine and synthesis of a photocatalytic chiral proline-based organocatalyst." Thesis, KTH, Organisk kemi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-293510.
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Photoredox catalysis applications for the purpose of new synthetic routes in organic and sustainable chemistry are hot topics in organic synthesis today. In the present study, the synthesis of a chiral proline-based organocatalyst functionalized with 10-phenyl-10H phenothiazine (PTH) photocatalytic moietiesis investigated and attempted for the first time. PTH, an organic photocatalyst, isstudied for its photocatalytic activity in different organic reactions, such as dehalogenation of aromatic halides and the pinacol coupling reaction between aromatic aldehydes. These transformations are otherwise difficult to achieve without a suitable catalyst and the reactions were performed with moderate to high yields.Applikationer av photoredox-katalys med syftet att generera nya syntetiska vägar inom organisk och hållbar kemi är populära ämnen i organisk syntes idag. I denna studien undersöktes för första gången syntesen av en kiral prolinbaserad organokatalysator som är funktionaliserad med fotokatalytiska enheter (10-fenyl-10H-fenotiazin (PTH)). Den fotokatalytiska aktiviteten av PTH studerades för olika organiska reaktioner, såsom t.ex. dehalogenering av aromatiska halider och pinacolkopplingar mellan aromatiska aldehyder. Dessa transformationer är annars svåra att uppnå utan en lämplig fotokatalysator och reaktionerna utfördes med måttliga till höga utbyten.
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Schlauderer, Florian Michael [Verfasser], and Karl-Peter [Akademischer Betreuer] Hopfner. "Structural and functional analysis of MALT1 inhibition by phenothiazine derivatives / Florian Michael Schlauderer ; Betreuer: Karl-Peter Hopfner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1125371641/34.
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Otteny, Fabian [Verfasser], and Birgit [Akademischer Betreuer] Esser. "Redoxaktive Polymere auf Basis von Phenothiazin, Phenoxazin, Phenazin und Terephthalat als Elektrodenmaterialien für Batterien." Freiburg : Universität, 2020. http://d-nb.info/1233599895/34.
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Schäfgen, Björn [Verfasser], and Werner R. [Akademischer Betreuer] Thiel. "Funktionalisierte mesoporöse Hybridmaterialien als Träger katalytisch aktiver Zentren sowie von redoxaktiven Phenothiazinen / Björn Schäfgen ; Betreuer: Werner R. Thiel." Kaiserslautern : Technische Universität Kaiserslautern, 2019. http://d-nb.info/1197055436/34.
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MICHELOT, GUENDAL. "Etude de la synthese de deux molecules d'interet industriel : l'acide 3-(r)-phenyl-butyrique et la 2-methylthio-phenothiazine." Rennes 1, 2001. http://www.theses.fr/2001REN1A003.
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L'objectif de ce travail est l'etude de la synthese de deux molecules d'interet industriel : l'acide 3-phenyl-butyrique et la 2-methylthio-phenothiazine. Ce travail est donc presente en deux parties distinctes. Dans la premiere partie, nous montrons que l'acces a l'acide 3-phenyl-butyrique peut se faire via une condensation de knoevenagel-cope entre l'acetophenone et le cyanacetate d'ethyle suivie d'une reduction de la liaison ethylenique puis de l'hydrolyse acide de l'intermediaire obtenu. L'etude du mecanisme de cette condensation de knoevenagel-cope, nous a permis de preciser l'origine d'un produit secondaire (une dihydropyridone) et d'etablir sa structure. Cette etude s'est revelee interessante sur le plan des applications car nous avons pu montrer pour la premiere fois que le milieu ch 3co 2h-ch 3co 2nh 4 est bien adapte pour realiser l'auto-condensation des cetones conduisant a la synthese de cetones ,-ethyleniques. Dans la seconde partie, nous avons examine plusieurs voies de synthese pour acceder a la 2-methylthio-phenothiazine, et notamment les thioalkylations en serie aromatique a partir de chlorures de sulfenyle et de montmorillonite comme catalyseur. Par cette methode, nous avons synthetise un diphenyl-sulfure nitre (le 1-methylthio-4-(2-nitro-phenylthio)-benzene) interessant puisque sa cyclisation par le phosphite de triethyle mene directement a la 3-methylthio-phenothiazine par suite d'une transposition de type smiles. La synthese de la 2-methylthio-phenothiazine a pu etre realisee avec succes par une reduction cyclisante du 1-methylthio-3-nitro-4-phenylthio-benzene.
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Kromm, Tanja [Verfasser]. "Mitochondriale Dysfunktion in der Pathogenese der Parkinson-Krankheit und der protektive Einfluss von Phenothiazin / Tanja Kromm." Mainz : Universitätsbibliothek Mainz, 2020. http://d-nb.info/1212145135/34.
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Dirksen, Elena [Verfasser], Thomas J. J. [Gutachter] Müller, and Klaus [Gutachter] Schaper. "Synthese neuartiger Acceptor-substituierter Phenothiazine als Systeme für photoinduzierten intramolekularen Elektronentransfer / Elena Dirksen ; Gutachter: Thomas J. J. Müller, Klaus Schaper." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1189901714/34.
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Daniel, Daniela. "Desenvolvimento de célula espectroeletroquímica em fluxo e sua aplicação analítica ao estudo e a determinação de derivados fenotiazínicos." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/46/46133/tde-13092006-145258/.
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O presente trabalho versa sobre o aperfeiçoamento e a avaliação de uma nova célula espectroeletroquímica de longo caminho óptico, com detecção espectrofotométrica in situ, na região do ultravioleta e visível, otimizada para operação em fluxo, sobretudo no modo FIA (Flow Injection Analysis). Monitoramento sensível e razoavelmente seletivo, além da facilidade de construção e adaptação à instrumentação comercial existente, foram características consideradas no aprimoramento da célula, que utiliza filmes de Au como eletrodos de trabalho, obtidos à partir de certos tipo de CDs regraváveis (Compact Disc-Recordable), colados sobre bases acrílicas e diretamente acomodados em cubetas convencionais, com 1 cm de caminho óptico, tornando seu custo de produção inferior a qualquer outro modelo proposto. Utilizando como sistemas modelo, a o-tolidina e o hexacianoferrato de potássio, foram avaliados parâmetros instrumentais tais como: potencial aplicado, vazão, volume injetado; repetibilidade e faixa de concentração de analito, com a finalidade de se estabelecer as melhores condições de trabalho e funcionamento da célula, tendo em vista sua aplicação analítica. Alta sensibilidade óptica, operação estável e reprodutível, além da possibilidade de se trabalhar tanto no modo estacionário como em fluxo, com a vantagem de se poder combinar a técnica à metodologia utilizada na análise por injeção em fluxo (FIA), foram algumas das características observadas para a célula construída. Desvendadas as potencialidades da célula, em busca de maior compreensão sobre os processos envolvidos, passou-se à investigação do mecanismo de oxidação de alguns derivados fenotiazínicos, através da realização de um estudo comparativo entre: a prometazina, a promazina e a clorpromazina, em diferentes meios de trabalho. A combinação de informações eletroquímicas e espectroscópicas obtidas in-situ contribuiu para melhor entendimento dos mecanismos envolvidos, revelando que, embora o meio de trabalho escolhido possa exercer significativa influência no mecanismo de oxidação, a estrutura da cadeia lateral é, neste caso, o fator preponderante na formação dos produtos de oxidação. Visando o desenvolvimento de novas metodologias para a quantificação de derivados fenotiazínicos em formulações farmacêuticas, foram realizados estudos com o propósito de definir as melhores condições de trabalho, bem como o efeito da presença de interferentes concomitantes. Os resultados obtidos para a determinação da prometazina no Fenergan (Rhodia-Farma) e no Lisador (Farmasa), e para a clorpromazina no Amplictil (Aventis), seja pela construção de curvas analíticas e/ou pelo método da adição de padrão, mostraram-se concordantes com os valores fornecidos pelos laboratórios fabricantes e comparáveis com os obtidos através da metodologia oficial. Para a prometazina os limites de detecção foram determinados em 1,3 10-6 mol L-1 e 3,0 10-5 mol L-1 para as medidas espectrofotométricas e eletroquímicas, enquanto os limites de quantificação foram estimados em 1,1 10-4 mol L-1 e 2,2 10-5 mol L-1 para as medidas eletroquímicas e espectrofotométricas, respectivamente. Para a clorpromazina, os limites de detecção foram de 7,6 10-5 mol L-1 e 4,1 10-5 mol L-1 para as medidas eletroquímicas e espectrofotométricas, enquanto os limites de quantificação foram determinados em 3,3 10-4 mol L-1 e 1,6 10-4 mol L-1 para as medidas eletroquímicas e espectrofotométricas, respectivamente. A dupla resposta proporcionada pela técnica empregada (amperométrica e espectrofotométrica) permite contornar os efeitos causados pela presença de interferentes eletroativos ou coloridos, contribuindo para a alta seletividade do método e melhor discriminação entre o sinal do analito e de interferentes.The present work is concerned with the enhancement and assessment of a novel long-optical-path spectroelectrochemical cell for in situ spectrophotometric detection in the ultraviolet and visible range, optimised for flowing operation, especially under FIA (Flow Injection Analysis) conditions. The sensitive and rather selective monitoring of electrolysed species present at the electrode-solution interface, together with simplicity of assembly and adaptation to existing commercial equipments, were some of the features targeted in the cell\'s improvement. The use of Au-film electrodes obtained from certain types of recordable CDs (Compact Disc-Recordable), attached onto acrylic supports in turn accommodated directly in conventional 1-cm optical-path cuvettes, makes the production of this cell cheaper than any other model so far proposed. O-tolidine and potassium hexacyanoferrate were employed as model systems for the assessment of instrumental parameters such as applied potential, flow rate, injected volume, repeatability and concentration range of the analyte, aiming at establishing the best working conditions for its application in analytical chemistry. High optical sensitivity, stable and reproducible operation, as well as the possibility of functioning either in the stationary or in flow modes, thus with the advantage of exploiting the FIA methodology, are some of the features observed for the cell. Further to highlighting the cell\' potentials and in order to seek a better understanding of the processes involved, the oxidation mechanism of a few phenothiazinic derivatives was investigated. Prometazine, promazine and chlorpromazine were comparatively studied in different media. The combination of the electrochemical and spectroscopic information obtained in situ contributed for a better comprehension of the mechanisms involved and revealed that the structure of the side chain is the key factor in the formation of the oxidation products, although the difference in the electrolytic medium is likely to play a significant role in the oxidation process. New analytical methodologies for the quantification of phenothiazinic derivatives in farmaceutical formulations were developed through studies focused on the definition of the optimum experimental conditions and on the effect of potential interfering species. Prometazine was determined in Fenergan (Rhodia-Farma) and in Lisador (Farmasa), whereas chlorpromazine was quantified in Amplictil (Aventis). The limits of detection (LOD) for promethazine were determined to be 1,3 10-6 mol L-1 and 3,0 10-5 mol L-1 for spectrophotometric and electrochemical measurements, while the limits of quantification (LOQ) were determined to be 1,1 10-4 mol L-1 and 2,2 10-5 mol L-1 for spectrophotometric and electrochemical measurements, respectively. For chlorpromazine, the limits of detection (LOD) were determined to be 7,6 10-5 mol L-1 and 4,1 10-5 mol L-1 for spectrophotometric and electrochemical measurements, while the limits of quantification (LOQ) were determined to be 3,3 10-4 mol L-1 and 1,6 10-4 mol L-1 for spectrophotometric and electrochemical measurements, respectively.The results obtained using both analytical curves and the standard addition methods, were consistent with the outcome of official methods and with the data supplied by the manufactures. The double response provided by the technique, amperometric and spectrophotometric, allows overcoming the interference of electroactive and colored species, hence turning this a highly selective method with an enhanced discrimination strength between the signal of the analyte and that of interfering species.
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Rechmann, Julian [Verfasser], Andreas [Gutachter] Erbe, and Axel [Gutachter] Rosenhahn. "Modification of metal surface electronic properties by phenothiazine-based SAMs / Julian Rechmann ; Gutachter: Andreas Erbe, Axel Rosenhahn ; Fakultät für Chemie und Biochemie." Bochum : Ruhr-Universität Bochum, 2020. http://d-nb.info/1204258538/34.
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Rechmann, Julian [Verfasser], Andreas Gutachter] Erbe, and Axel [Gutachter] [Rosenhahn. "Modification of metal surface electronic properties by phenothiazine-based SAMs / Julian Rechmann ; Gutachter: Andreas Erbe, Axel Rosenhahn ; Fakultät für Chemie und Biochemie." Bochum : Ruhr-Universität Bochum, 2020. http://nbn-resolving.de/urn:nbn:de:hbz:294-69146.
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Versäumer, Marina. "Supramolecular coordination cages based on bispyridyl-ligands with redox properties." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2016. http://hdl.handle.net/11858/00-1735-0000-002B-7C2F-E.
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Manuel, Christian. "Les neuroleptiques phénothiaziniques peuvent-ils induire une activité antimicrobienne circulante chez des patients traités ?" Paris 5, 1994. http://www.theses.fr/1994PA05P227.
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Alsaleh, Ajyal Zaki. "Spectral, Electrochemical, and Solar Cell Studies of Peripheral Modified Carboxy Zinc Porphyrins." Thesis, University of North Texas, 2019. https://digital.library.unt.edu/ark:/67531/metadc1505284/.
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Six peripherally meso-modified Zn (II) porphyrin sensitizer dyes are designed and their J-V performance in dye sensitized solar cell (DSSC) evaluated. Electron-donating groups including phenothiazine, carbazole and pyrene are used to modify the porphyrin macrocycle at the meso-carbon position(s). To compare the effect of donor substitution on the performance of the cells in terms of short circuit current (Jsc), light harvesting efficiency (LHE) and power conversion efficiency (η), two sets of sensitizers with different degrees of substitution are synthesized. One set of dyes (mono-substituted) have one electron donor at trans-position to the acceptor, while the second set (tri-substituted) dyes have three of the same type electron donor groups at 5, 10 and 15 meso-carbon positions making all the six dyes push-pull type sensitizers incorporating 4'-carboxyphenyl as an electron-acceptor/anchor group. Different spectroscopic and electrochemical methods are used to study the photophysical and electrochemical properties of the dyes, while the photovoltaic performance of their cells under 1.5 A.M is studied using solar simulator. Meso-substitution of Zinc (II) porphyrin with these small donor molecules is shown to improve the light harvesting character of the Zinc (II) porphyrin macrocycle in the UV-Vis absorption while at same time improving its fluorescence quantum yield, excited-state life time and electron donating potential. All these factors combined make these meso-modified dyes better sensitizers with suitable Δ0 Δ0, and much improved power conversion efficiencies (PCE) compared to unsubstituted Zn (II) porphyrin. In particular, as a result of the peripheral modification, a doubling in efficiency in the mono- substituted series (RA-200-Zn; η=^M 4.2%, Jsc= -13.13 mA cm-2, Voc=0.54 ) and tripling in the tri-substituted series ( tri-phenothiazine Zn (II) Porphyrin; η= 7.3%, Jsc= -18.15 mA cm-2, Voc= 0.55 ) compared to unsubstituted Zn (II) porphyrin (η= 2.11%, Jsc= -5.7 mA cm-2, Voc= 0.53 V) has been accomplished.
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Levi, Lucilla [Verfasser], Thomas J. J. [Akademischer Betreuer] Müller, and Klaus [Akademischer Betreuer] Schaper. "Synthese und Eigenschaften von Phenothiazinyl-Merocyaninen mit konjugierten und nichtkonjugierten Donoren für neuartige DSSC-Farbstoffe / Lucilla Levi. Gutachter: Thomas J. J. Müller ; Klaus Schaper." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1081767693/34.
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Meyer, Tim [Verfasser], Thomas J. J. [Akademischer Betreuer] Müller, and Klaus [Akademischer Betreuer] Schaper. "Phenothiazin-Merocyanine für farbstoffsensibilisierte Solarzellen - Diversitätsorientierte Ein-Topf-Synthese und Optimierung der elektronischen Eigenschaften / Tim Meyer. Gutachter: Thomas J. J. Müller ; Klaus Schaper." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1061121356/34.
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Godet-Bar, Thibault. "Synthèse et étude physico-chimique de nouveaux matériaux organiques d'électrode positive à base de phénothiazine pour les applications dans les accumulateurs au lithium." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENI022.
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L’objectif de cette thèse est de développer des matériaux organiques rédox à base de phénothiazine pour être utilisés à l’électrode positive des batteries lithium. Les matériaux organiques s’inscrivent en rupture des matériaux inorganiques coûteux et toxiques. Dans ce but, des matériaux rédox contenant l’unité phénothiazine ont été synthétisés, caractérisés. Leurs propriétés électrochimiques ont été analysées par dépôt sur électrode et par microélectrode à cavité, puis les plus prometteurs ont été testés en cellule lithium et sodium. La cible rédox choisie, la phénothiazine, a été polymérisée et substituée à un squelette phosphazène. Les tests en cellules ont mis en évidence la dissolution systématique du matériau et la nécessité d’empêcher ce phénomène rédhibitoire pour l’application batterie. Dans ce but, l’utilisation de polymères insolubles et de copolymères dotés d’une fonction post-réticulable ont permis d’augmenter significativement la cyclabilité et les performances énergétiques des cellules lithium. De plus, l’utilisation du sodium à l’électrode négative et d’anions peu lipophiles ont également permis de limiter cette contribution de dissolution. Une fonctionnalisation du carbone par la phénothiazine a également été investiguée par deux stratégies différentes. Dans les deux cas, un greffage a été réalisé avec succès. Les analyses électrochimiques ont permis de confirmer des propriétés électrochimiques très prometteuses de ces carbones modifiésThe aim of this work is to develop phenothiazine-based redox organic materials for lithium positive electrode. Comparatively to inorganic materials, organic ones can constitute clear break by decreasing the cost, toxicity and security issues while keeping good performances. In that purpose, redox materials involving phenothiazine moieties have been synthesized, characterized, then, their electrochemical properties have been analyzed electrochemically, the most promising ones have been tested in lithium and sodium cells. The redox target chosen, the phenothiazine, has been polymerized and functionalized onto phosphazene backbone. Cell tests showed material dissolution contribution has to be avoided. In this context, insoluble polyphenothiazine and cross-linkable copolymers were able to upgrade significantly the cyclability and the energetic performances of lithium cells. Moreover, sodium cells with a poor lipophilic anion showed lower dissolution contribution. Carbon grafting by phenothiazine has also been investigated. It has been performed by electrochemical and chemical means and has led to promising electrochemical performances