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1
Cilvez, Eda. "Design And Operation Of A Microwave Oven With Rotating Drums." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12610988/index.pdf.
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In this study it was aimed to design and operate a new system with sufficient number of rotating drums since rotation of turntable is incapable of providing uniformity. Effect of new design on final color values and moisture content were also investigated.
Macaroni beads were colored with CoCl2 solution and processed in a domestic microwave oven starting from 11.3±0.10% moisture content and L*= 41.1±
0.31 , a*= 8.5±
0.27 , b*= 5.3±
0.22 color value with turntable and the proposed design. In experiments 40%, 60%, 80% and 100% power levels and 1, 2 and 3 min processing times and 2 different locations were used. The average color values measured were not affected significantly by the locations studied inside the cavity for both operation types. The changes in color values were found to be significant with altering power level for both operation types. Time also changed average color values for samples processed on turntable and in rotating drums. The new design lowered the average L* values of the final product and kept the sample from burning. Average a* and b* values were not significantly affected by the operation type. The uniformity of final product in terms of color distribution was affected significantly by the operation type and the improvement in uniformity calculated quantitatively by means of variances and found out that the new design improved the color uniformity of the final product by 94.7%. The non-uniformity of the products processed on turntable was significantly changed with power level. Time or location did not affect uniformity significantly for both operation types. The final average moisture contents of samples processed on turntable were lower than the ones processed with the new design. That is, the rotating drums lowered the moisture removal compared to the turntable.
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Meijer, Helmut. "Research into and design of a digital sound sample library for acoustic drums." Thesis, Stellenbosch : University of Stellenbosch, 2004. http://hdl.handle.net/10019.1/16388.
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Thesis (M.Phil.)--University of Stellenbosch, 2004.ENGLISH ABSTRACT: Sound sample libraries represent the format in which huge collections of sampled sounds are made available for use within digital samplers and/or other digital audio workstations (DAW’s). Although in use for many years, little or no academic research has been done on the methodology of compiling a commercial sound sample library. In this endeavour, the factors influencing the design, recording and publishing of a sound sample library are investigated through the actual design of a drum sample library. The rationale behind the sampling of a drum kit is carefully depicted in the light of various other factors influencing the instrument, as well as being influenced by the instrument itself. A professional drummer was engaged to play a state-of-the art Gretsch acoustic drum kit. Samples of the kit, consisting of various individual instrument parts, were recorded in three locations within the Konservatorium of Stellenbosch University, for reasons carefully explained in the text. These numerous drum hits were mixed and cut into individual drum samples. The samples were mapped into a digital software sampler, GigaStudio, creating five distinct collections of drum samples that faithfully represent the quality of the drum kit, the recording rooms as well as the equipment used in the process. The outcome of the study is a professional product in the form of a Gretsch drum sample collection, prepared for commercial release. Many of the drum samples have already been used successfully in commercial music releases over the past 12 months. Whilst the drum sample library is currently being published, the product and documentation clearly depict the viability of the study in terms of the artistic and academic expectations that have been met. The study anticipates future research on the subject.
AFRIKAANSE OPSOMMING: Klankbiblioteke heet die formaat waarin versamelings van klankmonsters beskikbaar gestel word vir gebruik in digitale samplers1 en/of ander digitale klankprogrammatuur. Nieteenstaande die feit dat klankbiblioteke reeds jare in gebruik is, is geen studie waarin die ontwerp en saamstel van so ‘n biblioteek beskryf word, bekend nie. In hierdie navorsingsprojek word die faktore wat die ontwerp, opneem en vrystelling van ‘n klankbiblioteek beïnvloed bestudeer deur die skep van so ‘n biblioteek. Die oorwegings vir die keuse van ‘n tromstel is noukeurig uiteengesit in die lig van die faktore wat betrekking het tot, en wederkerig beïnvloed is deur die instrument en opname-omgewing. ‘n Professionele tromspeler is vir die projekdoeleindes gekontrakteer om ‘n Gretsch akoestiese tromstel te speel. Klankmonsters van die tromstel se individuele komponente is in drie lokale binne die Konservatorium van die Universiteit van Stellenbosch opgeneem, met redes soos uiteengestip in die teks. Klankopnames van die talle tromslae is gemeng en opgesny in individuele klankmonsters. Laasgenoemde is in GigaStudio, ‘n digitale sagteware sampler, gekarteer sodat vyf duidelik-onderskeibare klankveramelings geskep is. Hierdie versamelings lig die kwaliteit van die tromstel asook die verskeie opnamelokale en toerusting wat gebruik is duidelik uit. Die resultaat van die studie is ‘n professionele produk in die vorm van ‘n Gretsch kommersiële klankbiblioteek, waarvan verskeie klankmonsters reeds oor die afgelope 12 maande in plaaslike musiekvrystellings gebruik is. Hoewel die klankbiblioteek huidiglik vrygestel word, toon die produk en dokumentasie duidelik die artistiese en tegniese waardigheid van die studie. Die studie antisipeer toekomstige navorsings-moontlikhede wat uit die onderwerp mag voortspruit.
3
Sunkara, Koteswara Rao [Verfasser], and Eckehard [Akademischer Betreuer] Specht. "Granular flow and design studies in flighted rotating drums / Koteswara Rao Sunkara. Betreuer: Eckehard Specht." Magdeburg : Universitätsbibliothek, 2013. http://d-nb.info/1054420610/34.
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Sunkara, Koteswara Rao Verfasser], and Eckehard [Akademischer Betreuer] [Specht. "Granular flow and design studies in flighted rotating drums / Koteswara Rao Sunkara. Betreuer: Eckehard Specht." Magdeburg : Universitätsbibliothek, 2013. http://nbn-resolving.de/urn:nbn:de:gbv:ma9:1-3843.
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Slíva, Karel. "Návrh dvoutlakého horizontálního kotle na odpadní teplo." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2016. http://www.nusl.cz/ntk/nusl-254297.
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The focus of this thesis is a proposal of a horizontal dual-pressure heat recovery steam generator. The introductory part includes thermal calculation, as well as a design of the layout and a design of the heat transfer surfaces and the layout of the boiler. Individual chapters are broken down according to the outline of the proposal for the arrangement of the heating surfaces, according to the parameters of the flue gas and steam. The master thesis contains a scheme of a real heat transfer temperature diagram and it also includes the calculation of connecting and downcomer pipes and drums. The final part describes the calculation of the boiler draft loss. The main idea of the thesis is accompanied by the technical documentation of the drawing of the boiler.
6
Med, Lukáš. "Návrh dvoutlakého horizontálního kotle na odpadní teplo." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2016. http://www.nusl.cz/ntk/nusl-241924.
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This master's thesis deals with thermal calculation and design of proportions of calorific components of a heat recovery steam generator (HRSG), which is placed behind a combustion turbine, for given parameters of exhaust gases and requested parameters of steam. In the first chapters is described the design, layout of HRSG and the thermal calculation. The next parts deal with the design of flue-gas duct and each individual heating surface. Next section shows computations of dimensions of drums, flooding pipes, transferring pipes and all other outer pipes. The chosen materials are described in one of the last chapters and the last chapter deals with calculation of draft loss of steam generator.
7
Kjellberg, Nils. "Lätt på foten : En självobservationsstudie i fottekniksövning med dubbelpedalspel på trummor." Thesis, Karlstads universitet, Musikhögskolan Ingesund, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-68255.
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Syftet med arbetet är att jämföra två olika metoder för inlärning av fotteknik för spel vid trumset och hur de två olika metoderna påverkar trumspel. För att undersöka detta användes videoobservation samt loggbokförande under de sex veckor som undersökningsperioden varade. Varje vecka filmades tre olika övningstillfällen med varierande fokus. Studien grundar sig i det designteoretiska perspektivet. Resultatet av studien visade att olika metoder kan ge varierande resultat och att utforskandet av nya metoder kan ge positiva och oväntade resultat. Resultatet pekar även på att strategier och struktur ger positiva effekter vid övning. I diskussionsdelen diskuteras vilka resurser som varit mest givande för min utveckling samt hur en trummis måste vara medveten om sina begränsningar för att strategiskt kunna forma övning.The purpose of this study is to compare two different methods of learning foot-technique and how the two methods affect playing of the drums. To examine this video-observation filled an important role with complement of a journal during the six weeks of practice that were recorded. Each week there were three videos recorded with variating focus each video. The study is based on design theory which is described in the background chapter. The result of this study showed that different methods can result in variating outcome and it also showed that exploring new methods can give positive effects on your practice. The discussion revolves around what resources have been the most impactful for my own personal development and how one must be conscious of one’s own limitations to be able to create a successful plan of practice.
8
Maršík, Jaroslav. "Dvoutlaký horizontální kotel na odpadní teplo (HRSG)." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2015. http://www.nusl.cz/ntk/nusl-232157.
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The Master’s thesis dealing with design of heat recovery steam generator with two pressure levels is split into nine sections. The first section describes the design and the layout of HRSG. The second part deals with heat calculation. The third section deals with design of flue-gas duct. The fourth part describes designs of individual heating surfaces, including steam superheaters, vaporizers and economizer. Next section shows the real temperature diagram and choice of the materials. The seventh section describes the calculation of outer pipelines and the eighth part deals with the drums design. The last section deals with the calculation of draft loss of steam generator.
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Gupta, Sona. "Rational design and delivery of peptide drugs." Thesis, Bangor University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323850.
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Soldevila, Barreda Joan Josep. "Design of catalytic organometallic anti-cancer drugs." Thesis, University of Warwick, 2014. http://wrap.warwick.ac.uk/63808/.
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This thesis is concerned with the design of organometallic half sandwich complexes which can catalyse the conversion of oxidised coenzyme nicotinamide adenine dinucleotide to its reduced form. The coenzyme pair NAD+/NADH is involved in many biological processes, such as regulation of the redox balance, and DNA repair. Disturbance of the NAD+/NADH ratio can lead to cell death. In particular, cancer cells are under constant oxidative stress and therefore might be more susceptible to changes in the NAD+/NADH levels. A series of neutral Ru(II) complexes of the type [(η6-arene)Ru(N,N’)(L)] (arene = p-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), benzene (bn); N,N’ = N-(2-aminoethyl)-4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-toluensulfonamide (TsEn), or N-(2-aminoethyl)-4-methylensulfonamide (MsEn)) were synthesized and fully characterized. The complexes were shown by 1H-NMR to catalyse region-selectively the transfer hydrogenation of NAD+ to 1,4-NADH. Comparison of the turnover frequencies (TOF) for the complexes show a trend in which a decrease in catalytic activity with the arene ligand follows the order bn > bip > p-cym > hmb and TfEn > TsEn > MsEn. Complex [(η6-bn)Ru(TfEn)Cl] (12) was found to be the most active with a TOF of 10.4 h-1. The catalytic cycle for the transfer hydrogenation reaction was studied for complex [(p-cym)Ru(TsEn)Cl] (2). The monotosylate ethylenediamine Ru(II) complexes were used to carry out, for the first time, transfer hydrogenation reactions in cellulo (A2780 ovarian cancer cells) using formate as a hydride source. The antiproliferative activity of six complexes on co-administration with non-toxic doses of sodium formate were studied. A significant potentiation of the antiproliferative activity by formate was observed. The concentrations of NAD+ and NADH in cells showed an important reduction in the NAD+/NADH ratio. This study demonstrates that it may be possible to use catalytic transfer hydrogenation as a strategy for multi-targeted redox mechanisms of action for anticancer drugs. In order to compare the anticancer mechanism of the monotosylate ethylenediamine Ru(II) complexes with the corresponding ethylenediamine (en) complexes, DNA binding studies were carried out. The complexes were shown to bind to nucleobases only moderately strongly and no direct coordination to calf thymus DNA was observed. The complexes can destabilize DNA, but they display low affinity towards DNA, which suggests that DNA is probably not involved in the mechanism of these family of compounds. Interaction of complex [(p-cym)Ru(TsEn)] (2) with glutathione (GSH) was also studied. The complex undergoes ligand substitution. Two Ru(II) dimers were formed as the main products of the reaction: ([((p-cym)Ru)2(μ-GS)3] and [((p-cym)Ru)2(μ-GS)2]). These dimers share structural similitudes with other reported Ru(II) arene anticancer drugs, which suggests that they could be responsible for the moderate antiproliferactive activity of complex 2. A series of CpxRh(III) (CpX = CpXPhPh, CpXPh or Cp*) complexes containing en or TfEn were synthesised and fully characterised. The complexes were shown to catalyse regioselectively the transfer hydrogenation of NAD+ to 1,4-NADH with higher TOF than their Ru(II) analogues. Rh(III)-en compounds were shown to be more active than the Rh(III)-TfEn analogues. The nature of the Cpx ring was shown to influence significantly the catalytic activity of the complexes following the trend: CpXPhPh > CpXPh > Cp*. Complex [(CpXPhPh)Rh(en)Cl]+ (19) was the most active, with a TOF of 24.2 h-1. The catalytic cycle for the transfer hydrogenation reaction was studied using complex [(Cp*)Rh(en)Cl]+ (17) and compared to that of the Ru(II) analogues, and was found to be similar. Antiproliferative activity of the complexes in combination with formate, in A2780 cells, was investigated, but the potentiation due to the transfer hydrogenation was much lower than that obtained with Ru(II) compounds.
11
Zhang, Liang. ""Fleximers" design and synthesis of a new class novel shape-modified nucleosides." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/26207.
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Deanda, Felix. "Development and application of software tools for computer-assisted drug design /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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Young, Charlene Rebecca. "Rational drug design : an information driven approach to the design of an anthracycline analog /." [Boise, Idaho] : Boise State University, 2009. http://scholarworks.boisestate.edu/td/10/.
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Munday, Dale Leslie. "Design, development and evaluation of encapsulated oral controlled release theophylline mini-tablets." Thesis, Rhodes University, 1991. http://hdl.handle.net/10962/d1003255.
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Conventional solid dosage forms often lead to fluctuations which exceed the maximum safe therapeutic level and/or decline below the minimum effective level. It is recognised that many drugs for chronic administration should be administered on a schedule that maintains plasma drug concentration within the therapeutic window. Research in controlled release dosage forms aims at designing a system with a zero-order input (eg, ideally to deliver 8.33% of the dose per hour over a 12 hour duration), producing steady state plasma drug levels. Oral dministration of drugs prepared as a controlled release formulation is extremely popular, and has attracted the attention of pharmaceutical scientists during the last decade. This has been due to the simultaneous convergence of various factors (eg, discovery of novel polymers and devices, better understanding of formulation and physiological constraints, expiration of existing patents, prohibitive cost of developing new drug entities), involved in the development of these delivery systems. Controlled release oral products can be formulated as single or multiple unit dosage forms and the relative merits of multiple unit forms with their own rate controlling systems are well established. This work describes the development of a relatively inexpensive multiple-unit capsule dosage form of theophylline containing coated mini-tablets for drug delivery throughout the gastrointestinal tract. Preformulation studies on theophylline anhydrous included solubility and dissolution rate determinations. Techniques including X-ray powder diffraction, differential scanning colorimetry and infrared spectroscopy provided no evidence of true polymorphism after recrystallisation from various solvents. However, scanning electron micrographs showed the effects of solvent polarity and cooling rate on the size and shape of recrystallised particles. Theophylline granules were manufactured by using various binders and were film coated by fluidised bed technology with various proportions of ethylcellulose, containing varying amounts of PEG 1540. In vitro release rates were dependent upon coating thickness and the proportion of PEG, which, being water soluble, created pores in the coating during dissolution studies as observed by a scanning electron microscope. However, substantial proportions of the drug remained unreleased from the granules. In order to overcome the problems of drug retention, plain granules were used and theophylline mini-tablets (3 mm diameter, weighing 15 - 20 mg) were manufactured and film coated with various Eudragits ® and other polymeric mixtures (soluble and insoluble). In vitro dissolution profiles from samples enclosed in hard gelatin capsules were determined using the USPXXI paddle apparatus in test media at pH 1.2 (HCI), pH 5.4 and 7.4 (phosphate buffers) at 37'C. Monitoring of in vitro theophylline release over 12 h, under identical hydrodynamic conditions, showed that the dissolution rate at pH 1.2 is substantially greater (95% of total drug content released in < 10 h) than that in phosphate buffers. The maximum release after 12 h was approximately 20 and 30% of total drug content of the tablet at pH 5.4 and 7.4, respectively. However, in vivo bioavailability after oral administration of tablets to rabbits corresponded to over 95% of total drug, compared with the same dose administered intravenously. The retarded drug release during in vitro dissolution in phosphate buffer was attributed to a possible interaction of phosphate ions with theophylline molecules at the tablet core-coat interface. These findings indicate that both rate and extent of theophylline release from the slow release coated mini-tablets are highly sensitive to phosphate buffers. The data also emphasise the usefulness of an animal model for assessment of in vivo drug release and subsequent absorption during the development of modified release dosage forms. Mini-tablets were subjected to isothermal and cyclic stresses to reach conditions for up to 6 months at different temperatures and relative humidity. The film integrity was maintained but ageing of the coating occurred which impeded dissolution. Reduced drug release was temperature related while the effect of relative humidi% was insignific~t. Encapsulated mini-tablets (uncoated and coated with Eudragit RL and RS 2% w/w) equivalent to a 300 mg dose, were evaluated both in vitro and in vivo using beagle dogs. The pharmacokinetic parameters from single and multiple dose studies showed several advantages over Theo-Dur® 300 mg tablets. Precise dosage titration is possible by careful adjustment of the number of encapsulated mini-tablets. This multiple unit mini-tablet delivery system will allow for greater flexibility in dosage adjustment compared to the currently available preparations, allowing individualised fine dose titration in those patients requiring therapeutic drug monitoring. The developmentof the multiple unit mini-tablet formulation appears to provide an optimal dosage form with maximum flexibility in respect of dose, duration range and ease of production.
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Haule, Ambrose Francis. "Design of tryptophan analogues as novel tryptanocidal drugs." Thesis, University of Sunderland, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277923.
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Searle, Natalie Louise. "Design and synthesis of novel endoperoxide antimalarial drugs." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366699.
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Duffy, Judith Clare. "Design of novel non-steroidal anti-inflammatory drugs." Thesis, Liverpool John Moores University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521744.
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Cochrane, Wolf. "In silico synthesis of analogous lead libraries for drug design by molecular enumeration." Diss., Pretoria : [s.n.], 2007. http://upetd.up.ac.za/thesis/available/etd-04212008-135220/.
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Lloyd, Edward John, and mikewood@deakin edu au. "A common structural basis for central nervous system drug design." Deakin University. School of Biological Sciences, 1986. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20050902.115505.
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The main theme of this thesis is that there is a common structural basis for drugs acting on the central nervous system (CNS), and that this concept may be used to design new CNS-active drugs which have greater specificity and hence less side-effects.
To develop these ideas, the biological basis of how drugs modify CMS neurotransmission is described, and illustrated using dopaminergic pathways. An account is then given of the use of physicochemical concepts in contemporary drug design. The complete conformational analysis of several antipsychotic drugs is used to illustrate some of these techniques in the development of a model for antipsychotic drug action.
After reviewing current structure-activity studies in several classes of CNS drugs (antipsychotics, anti-depressants, stimulants, hal1ucinogens, anticonvulsants and analgesics), a hypothesis for a common structural basis of CNS drug action is proposed- This is based on a topographical comparison of the X-ray structures of eight representative CNS-active drugs, and consists of three parts: 1.there is a common structural basis for the activity of many different CNS-active drug classes; 2. an aromatic ring and a nitrogen atom are the primary binding groups whose topographical arrangement is fundamental to the activity of these drug classes;
3. the nature and placement of secondary binding
determines different classes of CNS drug activity. A four-Point model for this common structural basis is then defined using 14- CNS-active drug structures that include the original eight used in proposing the hypothesis. The coordinates of this model are: R1 (0. 3.5, 0), R2 (0, -3.5, O), N (4.8. -0.3, 1.4), and R3 (6.3, 1.3, 0), where R1 and R2 represent the point locations of a hydrophobic interaction of the common aromatic ring with a receptor, and R3 locates the receptor point for a hydrogen bond involving the common nitrogen, N. Extended structures were used to define the receptor points R1, R2 and R3, and the complete conformational space of each of the 14 molecules was considered.
It is then shoun that the model may be used to predict whether a given structure is likely to show CNS activity: a search over 1,000 entries in the current Merck Index shows a high probability (82%) of CNS activity in compounds fitting the structural model.
Analysis of CNS neurotransmitters and neuropeptides shows that these fit the common model well. Based on the available evidence supporting chemical evolution, protein evolution, and the evolution of neurotransmitter functions, it is surmised that the aromatic ring/nitrogen atom pharmacophore proposed in the common model supports the idea of the evolution of CNS receptors and their neurotransmitters, possibly from an aromatic amine or acety1cho1ine acting as a primaeval communicating molecule.
The third point in the hypothesis trilogy is then addressed. The extensive conformation-activity analyses that have resulted in well-defined models for five separate CNS drug classes are used to map out the locations of secondary binding groups relative to the common model for anti-psychotics, antidepressants, analgesics, anticholinergics, and anticonvulsants. With this information, and knowledge derived from receptor-binding data, it is postulated that drugs having specified activity could be designed.
In order to generate novel structures having a high probability of CNS-activity, a process of drug design is described in which known CNS structures are superimposed topographically using the common model as a template. Atoms regarded as superfluous may be selectively deleted and the required secondary binding groups added in predicted locations to give novel structures.
It is concluded that this process provides the basis for the rational design of new lead compounds which could further be optimized for potent and specific CNS activity.
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Attardo, Giorgio G. (Giorgio Giovanni). "Drug design and synthesis of novel heteroanthracycline antitumor drugs." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74641.
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Novel heteroanthracycline antitumor drugs were designed based on structure activity relationship studies and known mechanisms of drug action. Their preparation required the development of a general synthetic approach.After extensive studies, three methodologies were developed for the general synthetic plan. The first method involved photoenolisation of 2,5-dimethoxybenzaldehyde and SO$ sb2$ entrapment of the o-quinodimethane to give 4,7-dimethoxy-1-hydroxy-1,3-dihydrobenzo(2,3-c) thiophene-2,2-dioxide. This compound served as a general intermediate towards the synthesis of several heteroanthracyclinones. It could be reduced to the oxathiin-2-oxide derivative which thermally extruded SO$ sb2$ to yield the o-quinodimethane. Reentrapment of this latter intermediate with various glyoxalates gave key isochroman derivatives. The second method is an improvement over the first. Isochromandiones with a C-1 hydroxyl functionality were prepared from oxidative demethylation of 1-hydroxyisochromans. These were obtained after acid hydrolysis of the coupling products between epoxides and the cuprate of 2,5-dimethoxy-6-methylbenzaldehydedioxane acetal. The third method involved a sequential cycloaddition routine with two o-quinodimethanes.
By combining newly developed techniques with known methods, a general synthetic plan was developed. Consequently, the total synthesis of six tetracyclic structural hybrids of the naphthoquinone(2,3-c) pyranyl class of antibiotics was accomplished; along with the total synthesis of (R) and (S) 1-(4$ sp prime$-O-p-nitrobenzoyl-N-trifluoroacetyldaunosamine)-$ 1,3$-dihydrothioxantho(2,3-c) thiophene-2,2-dioxide, p-nitrobenzyl(5,12-dihydroxy-3,4-dihydrothioxantho(2,3-c) and (3,2-c) pyran-3-yl)formate, and eight novel heteroanthracyclines with the 5,12-dioxo-2,3,5,12-tetrahydroanthraceno(2,3-c) pyranyl backbone. The diastereomeric mixture of (1$ sp prime$S, 1R, 3S) and (1$ sp prime$S, 1S, 3R) methyl(11-hydroxy-1-$(2 sp prime,3 sp prime,6 sp prime $-trideoxy-3-trifluoroacetamido-L-lyxohexopyranose)-$5,12 $-dioxo-3,4,5,12-tetrahydroanthraceno(2,3-c) pyran-3-yl) formate was found to possess equipotent antileukemic activity to doxorubicin with no cross resistance.
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Ma, Haiqiu. "The formulation, manufacture and evaluation of capsules containing freeze-dried aqueous extracts of Leonotis Leonorus or Mentha Longifolia." Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_3777_1181559333.
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Leonotis leonorus and Mentha longifolia are two herbs commonly used in South Africa, mostly in oral liquid dosage forms. Several disadvantages are associated with these traditional dosage forms which can perhaps be remedied by using an appropriate oral solid dosage form, provided the actual plant material in the latter still resemble, as closely as possible, the traditionally used material and provide products of suitable pharmaceutical quality. The objectives of this study were to prepare and evaluate the pharmaceutical suitability of the freeze-dried aqueous extracts of Leonotis Leonorus and Mentha Longifolia as plant raw material for the capsule dosage of these two therapies and to formulate and manufacture capsules of Leonotis Leonorus and Mentha Longifolia aqueous extract that would contain amounts of the plant materials equivalent to that found in their traditional liquid dosage forms, and have immediate release characteristics and suitability stability.
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Thovarai, Vishal. "In silico drug design of potential novel anti malarial agents /." Online version of thesis, 2009. http://hdl.handle.net/1850/8689.
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Lang, Allan M. "An investigation into heavy vehicle drum brake squeal." Thesis, Loughborough University, 1994. https://dspace.lboro.ac.uk/2134/7447.
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Many mechanisms have been suggested for brake squeal over many years. In order to identify the most appropriate of these mechanisms, an experimental investigation has been carried out to define in detail the vibration characteristics of a squealing heavy vehicle air operated drum brake on both a vehicle and a laboratory brake test rig. This required the development of a novel 'scanning' technique for the modal analysis of the rotating drum, which showed the presence of well-defined complex wavelike modes. From these results, the dynamic behaviour of the drum, in particular, is found to be in good qualitative agreement with the predictions of a simple 'binary flutter' mechanism of squeal. Based on the role of rotor symmetry in this mechanism, a means of decoupling, flutter modes is developed involving a reduction in the rotational symmetry of the drum by means of attaching masses in a defined pattern at its periphery. It is shown theoretically that such decoupling would be expected to increase the dynamic stability of the brake, and experimental application of the technique confirms its effectiveness in reducing or eliminating squeal. Practical design aspects of reducing the rotational symmetry of the drum are considered, using finite element modelling, and it is also shown that the technique can be effective in other types of vehicle brake, such as disc brakes and hydraulic drum brakes. The simple lumped parameter models used in the above work are inadequate as brake design tools, however, and so a novel application of finite element modelling is used to extend the principle of the binary flutter mechanism to a more detailed model of a complete brake. This is shown to be capable of predicting known features of squeal and may be used as a brake design tool for both the brake structure and the friction material.
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McCallum, Emma Clare. "Adaptive phase II clinical trial design using nonlinear dose-response models." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709013.
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Yeap, S. K. "The design of tyrosinase inhibitors as novel chemotherapeutic agents." Thesis, University of Sunderland, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378608.
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Zhang, Huarui. "Design, synthesis and activity evaluation of novel exosome inhibitors." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/849.
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Background: Exosomes are extracellular vesicles (EVs) that produced in the endosomal compartment of most eukaryotic cells, and have observed increasing attentions over the past decades. They play important roles in cell- to-cell communications, they can carry varieties of substances, like proteins, nucleic acids and lipids, to the target cells they encounter. These cargos could influence the function of recipient cells. This novel mode of intercellular communication is found to be of critical importance to many cellular activities. However, exosomes are involved in various diseases processes. Tumor- derived exosomes could promote cancer progression, and our preliminary study indicated that exosome released from osteoclasts could inhibit bone formation. We also found that osteoarthritis (OA) progression in OA mice could be attenuated by inhibiting exosomes released by osteoclasts. Therefore, inhibition of exosome release has potential value in the treatment of diseases. The exosome release is under control by RAB27A, which is a protein involved in protein transport and signal transduction. It is reported that a compound named Nexinhib20 could selectively inhibit RAB27A, but this compound is highly toxic to RAW264.7 cells, which IC 50 is 1.5 µM. Therefore, for safety concerns, it has to be chemically modified to reduce toxicity. Aim: (1) To design and synthesize a series compounds based on the structure of Nexinhib20. (2) To evaluate the toxicity and exosome inhibiting activity of the synthesized compounds and discuss the structure-activity relationships (SAR) of them. Materials and Methods: Nexinhib20 derivatives were synthesized by aldol reaction. The cytotoxicity of these compounds was evaluated by MTT assay. The exosome inhibiting activity of these compounds was evaluated through exosome isolation and quantitation. Result: A series of compounds were synthesized and their structures were confirmed by LC-MS and NMR. The structure-activity relationships of these compounds were discussed, and the results showed that compounds A3, A23 and B2 exhibited lower toxicity compared to Nexinhib20 and strong exosome inhibiting ability. Conclusion: The results of this project indicate that A3, A23 and B2 exhibited low toxicity and good exosome inhibiting activity. Based on this, further chemical modification could be applied to develop new exosome inhibitors with better efficacy
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Mungongo, Singfrid Gasper. "The design, synthesis and biological evaluation of novel antitrypanosomal drugs." Thesis, University of Sunderland, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284073.
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Carmichael, Samantha Jane. "Optimisation of study design in the pharmacokinetics of anticancer drugs." Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/23290.
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"Optimal sampling strategies" are based upon the concept of 'information-rich' times within a concentration-time profile. In this thesis, the selection of optimal sampling times was based on sensitivity analysis and applied to the one and two-compartment PK models. Simulation studies were used to show that parameter estimates obtained using an optimal design method with a reduced number of samples were as good as, if not better than, those obtained from PK studies in which the sampling times were selected empirically. In addition, the effect of adding sampling windows around the "optimal" times offered improved estimation of the inter-subject variability parameters, when compared to designs with fixed sampling times. This result has particular relevance in a clinical setting where a sample may not be collected at the stipulated time, but is still useful in the analysis if the "actual" sampling time is recorded accurately. Further simulations were based on published sampling designs for the anticancer drug carboplatin, and these were used for comparison with the results when an "optimal design" was used. Finally, a population analysis was carried out on data from a phase I clinical trial of the broad-spectrum neuropeptide antagonist, Antagonist G. The parameter values were used to design on "optimal" sampling strategy. As the sample times of the optimal strategy were different to those used in the clinical study, further simulations were used to compare the design. Using sensitivity analysis to design sampling strategies for population PK studies allowed the selection of a minimum number of sampling times, but still resulted in accurate estimation of the parameters of the one and two-compartment PK models. These sampling times provide a basis for PK study design, around which further samples could be added to improve the identification of the model and also the estimation of parameters and their inter and intra-subject of variability.
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Gibson, Victoria. "Design, synthesis and evaluation of anthraquinone-oligodeoxynucleotide conjugates." Thesis, University of Sunderland, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242343.
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Ward, D. J. "Further development of methods for the computer-aided design of neuropeptide-based drugs." Thesis, University of Manchester, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280534.
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Ling, Xiang. "Adaptive design in dose-response studies." Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1133365136.
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Mosley, Sylvester L. "Base-modified carbocyclic nucleosides as medicinal agents." Thesis, Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/27041.
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Gustafsson, Jörgen. "Synthesis of cyclohexenedicarbaldehydes and studies of their biologic activity." Lund : Organic Chemistry 2, Lund Institute of Technology, University of Lund, 1994. http://books.google.com/books?id=ULpqAAAAMAAJ.
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Lu, Jun. "Toward the next generation of smart anti-tumor drugs: a highly water-soluble Nucleolin Aptamer-Paclitaxel conjugate with a Cathespin B-labile linker for tumor-specific targareting in ovarian cancer." HKBU Institutional Repository, 2017. https://repository.hkbu.edu.hk/etd_oa/440.
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Paclitaxel (PTX) is among the most commonly used first-line drugs for cancer chemotherapy. However, its poor water solubility and indiscriminate distribution in normal tissues remain clinical challenges. Here we designed and synthesized a highly water-soluble nucleolin aptamer-paclitaxel conjugate (NucA-PTX) that selectively delivers PTX to the tumor site. By connecting a tumor-targeting nucleolin aptamer (NucA) to the active hydroxyl group at 2' position of PTX via a cathepsin B sensitive dipeptide bond, NucA-PTX could remain stable and inactive in the circulation. The tumor-recognition component NucA facilitates the uptake of the conjugated PTX specifically in tumor cells. Once inside cells, the dipeptide bond linker of NucA-PTX will be cleaved by cathepsin B and then the conjugated PTX will be released for action. The stability of NucA-PTX in human serum and the cathepsin-B dependent release of the conjugated PTX in tumor cells were verified by monitoring the fluorescence resonance energy transfer (FRET) of a dual fluorescence-labeled conjugate FAM-NucA-PTX-Rd. In addition, the PTX conjugation did not considerably affect the binding affinity between NucA and its target protein nucleolin, which was supported by both molecular dynamic simulation and isothermal titration calorimetry (ITC). The NucA modification was shown to facilitate the uptake of the conjugated PTX in ovarian cancer cells mainly by macropinocytosis in a nucleolin expression-dependent manner. Moreover, the NucA modification increased the in vitro cytotoxicity and mitosis inhibition of the conjugated PTX in ovarian cancer cell lines. The in vivo data collected from a human xenograft model of ovarian cancer demonstrated that the NucA modification facilitated the selective accumulation of the conjugated PTX in ovarian tumor tissue, and subsequently resulting in notably improved antitumor activity and reduced toxicity.
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Brown, Kieran Pearse. "BUILDING A "DRUM SET": DESIGNING THE SCENERY FOR SAM SHEPARD'S FOOL FOR LOVE." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/theses/1529.
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I designed the set for Fool For Love by Sam Shepard in the McLeod Theater, Fall Semester 2013 for my thesis production. Fool For Love Is a short and intense hyper-realistic play about two lovers with a dark past. The entire play takes place in one extended scene in a motel room on the edge of the desert. Eddie tries to win May back, while she tries to free herself from her need to go back to him. The Old Man is a figure outside of reality that intrudes on the play, the father they share and the source of the shame in their relationship. A suitor, Martin, appears to set this combustible mixture off. I designed a cramped and derelict space which pushed the auditory surrealism of the play and made the experience as intimate and intense as I could for the audience. Chapter 1 contains me research and initial response to both the script and the thesis process. Chapter 2 walks through the process of designing and building the show. Chapter 3 reflects on my performance overall. Chapter 4 is a deeper look into design communication, a weakness this process revealed in my work.
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Elmagbari, Fatin M. Ali. "Synthesis and design of ligand copper complexes as anti-inflammatory drugs." Doctoral thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15767.
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Rheumatoid arthritis is a debilitating disease for which there is no cure. Copper has been used for centuries to alleviate the inflammation associated with the disease. The aim of this research was to design and test new ligands which are able to promote the percutaneous absorption of copper and/or mobilize endogenous copper reserves. Formation constants of H+, Cu(II), Ni(II) and Zn(II) with five low molecular ligands 2-((2-aminoethyl)amino)-N-(pyridin-2- ylmethyl)acetamide) [H(555)NH2], 2-((2-dimethyl-amino)ethyl)amino)-N-(pyridin-2-ylmethyl) acetamide [H(555)NMe2], N-(2-aminoethyl)-N'-(pyridin-2-ylmethyl)ethanediamide [H2(555)NH2], 3-(2-aminoacetamido)-N-(pyridin-2-ylmethyl)propanamide [H2(565)NH2], 3-amino-N-(pyridin-2-lmethyl)-propanamide [H(56)NH2] were measured at 25±0.01oC and at an ionic strength of 0.15M (NaCl) using glass electrode potentiometry. The structures of the different Cu(II) species formed with these ligands were investigated using ultraviolet-visible (Uv-visible), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography as well as molecular mechanics calculations. The Uv-visible spectra obtained for the different species in solution were typical of tetragonally distorted Cu(II) complexes. The active binding sites were identified as the pyridine nitrogen, the amide nitrogen and the terminal amino group. The pyridine nitrogen was involved in coordination first, followed by the amide and then the terminal amine groups. The X-ray crystal structure of two of the Cu(II) complexes were solved; one formed a rectangular pyramidal geometry and the other a distorted square planar geometry. Molecular mechanics was used to determine the lowest energy conformation of different possible geometries. Since the preferred route of administration is through the skin, the rate of dermal absorption and the bioavailability of copper are important. For this reason, the drugs were designed so that they could be administered dermally and be selective for Cu(II) so that they do not affect the speciation of other metal ions in blood plasma. Speciation calculations using a blood plasma model were used to estimate the complexing ability of the ligands in vivo. This result showed that [H(555)NH2] was the best at mobilising copper in vivo.
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O'Daniel, Peter Ivo. "Exploring structural diversity in nucleoside and nucleic acid drug design." Diss., Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-08252005-130946/.
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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006.Barefield, E. Kent, Committee Member ; Beckham, Haskell W., Committee Member ; Doyle, Donald F., Committee Member ; Weck, Marcus, Committee Member ; Seley, Katherine L., Committee Chair.
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Long, Stephen. "Combinatorial methods in drug design : towards modulating protein-protein interactions./." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17525.pdf.
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Tripathi, Ashutosh. "DEVELOPMENT OF HINT BASED COMPUTATIONAL TOOLS FOR DRUG DESIGN: APPLICATIONS IN THE DESIGN AND DEVELOPMENT OF NOVEL ANTI-CANCER AGENTS." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1866.
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The overall aim of the research is to develop a computational platform based on HINT paradigm for manipulating, predicting and analyzing biomacromolecular-ligand structure. A second synergistic goal is to apply the above methodology to design novel and potent anti-cancer agents. The crucial role of the microtubule in cell division has identified tubulin as an interesting target for the development of therapeutics for cancer. Pyrrole-containing molecules derived from nature have proven to be particularly useful as lead compounds for drug development. We have designed and developed a series of substituted pyrroles that inhibit growth and promote death of breast tumor cells at nM and μM concentrations in human breast tumor cell lines. In another project, stilbene analogs were designed and developed as microtubule depolymerizing agents that showed anti-leukemic activity. A molecular modeling study was carried out to accurately represent the complex structure and the binding mode of a new class of tubulin inhibitors that bind at the αβ-tubulin colchicine site. These studies coupled with HINT interaction analyses were able to describe the complex structure and the binding modes of inhibitors. Qualitative analyses of the results showed general agreement with the experimental in vitro biological activity for these derivatives. Consequently, we have been designing new analogs that can be synthesized and tested; we believe that these molecules will be highly selective against cancer cells with minimal toxicity to the host tissue. Another goal of our research is to develop computational tools for drug design. The development and implementation of a novel cavity detection algorithm is also reported and discussed. The algorithm named VICE (Vectorial Identification of Cavity Extents) utilizes HINT toolkit functions to identify and delineate a binding pocket in a protein. The program is based on geometric criteria and applies simple integer grid maps to delineate binding sites. The algorithm was extensively tested on a diverse set of proteins and detects binding pockets of different shapes and sizes. The study also implemented the computational titration algorithm to understand the complexity of ligand binding and protonation state in the active site of HIV-1 protease. The Computational titration algorithm is a powerful tool for understanding ligand binding in a complex biochemical environment and allows generating hypothesis on the best model for binding.
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Yang, Chunping. "Rotating Drum Biofiltration." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1092668752.
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Bahceci, Suleyman. "The electron-conformational method of molecular modeling in drug design and structure-activity relationships /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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Isaacs, Nasreen. "Formulation and process optimisation of ethionamide 250 MGtablets using quality by design principles." Thesis, Nelson Mandela Metropolitan University, 2015. http://hdl.handle.net/10948/3979.
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The traditional approach of Quality by Testing (QbT) limits the assurance of product quality to in-process and post-production testing. To overcome these limitations, a more proactive and systematic means to product development and optimisation is required. Quality by Design (QbD) is an example of such an approach which focuses on understanding the product and its manufacturing process and emphasises that quality should be built into the product and not merely tested. The study aims to optimise ethionamide tablets, an immediate release oral solid dosage form using QbD.
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Sheeka, Hendrika Maria. "Design and synthesis of novel nucleotide pro-drugs as anti-HIV agents." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295004.
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Moorad, Razia. "Computer-aided drug design and the biological evaluation of anti-cancer drugs." Doctoral thesis, University of Cape Town, 2016. http://hdl.handle.net/11427/20715.
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Computer-aided drug design has become a promising alternative to high-throughput screening by identifying potential hits in silico for in vitro evaluation. In this study a combination of ligand-based and structure-based virtual screening was performed to identify in silico hits. This was based on finding similar inhibitors to 6-amino-4-(4-phenoxyphenylethylamino) quinazoline, a potent inhibitor of the Nuclear Factor kappa B (NF-κB), a transcription factor that has a pivotal role in cancer survival and Pentamidine, an anti-parasitic drug that has recently been demonstrated to possess tumour-killing activity. A hierarchical methodology consisting of a similarity search followed by structure-based virtual screening of the ZINC database was performed. In order to perform the docking studies, binding sites for 6-amino-4-(4-phenoxyphenylethylamino) quinazoline on the NF-κB/IκBα complex were identified through blind docking. In addition, the National Cancer Institute (NCI) database was screened, utilising existing structure-activity relationship data from literature. A pharmacophore search was designed to test the hypothesis of the structural features necessary for activity as seen with quinazoline inhibitors of NF-κB. No virtual hits from the ZINC database were confirmed with in vitro activity. On the other hand, three compounds identified from the pharmacophore search were confirmed to inhibit cancer cell proliferation in vitro, with compound NSC727152 demonstrating the most potent activity. In order to determine if NSC727152 acted similarly to 6-amino-4-(4-phenoxyphenylethylamino) quinazoline by inhibiting NF-κB, the effects of NSC727152 on the expression of NF-κB targeted genes, including the Growth Arrest and DNA Damage 45 (GADD45) α and γ and the Interleukin 6 (IL-6) genes were evaluated. GADD45 α and γ have been shown to be regulated by NF-κB during cancer progression and aberrant IL-6 gene expression has been implicated in cancer progression and mortality and its expression is at least partially mediated via constitutive activation of NF-κB. In this study, it has been demonstrated that GADD45 α and γ are upregulated after treatment with NSC727152. A down-regulation of the IL-6 promoter activity and mRNA expression in cancer cells treated with NSC727152 has also been demonstrated in this study. However, no hits similar to Pentamidine were confirmed with in vitro activity. In conclusion, the compound NSC727152 has been shown to inhibit NF-κB and further analysis is necessary to determine its full potential as an NF-κB inhibitor.
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Clement, Ella Chow. "Design and Syntheses of Potential Drugs Based on GABA(A) Receptor Pharmacophores." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/28271.
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Numerous previous studies of GABAAR ligands have suggested that GABAAR agonists must be zwitterionic and feature an intercharge separation similar to that of GABA (approx. 4.7-6.0 Ã ). We have demonstrated that monomeric, homodimeric and heterodimeric non-zwitterionic GABA amides are partial, full, or superagonists at the murine GABAA receptor (GABAAR). The agonism of these GABA amides is comparable to that of THIP, as shown by in vitro assay results. The assay data indicate that the agonism of GABA amides is tether length-dependent. Optimum agonism is achieved with a tether length of four methylenes in GABA amide dimers and in GABA amides bearing pendant amide or amino groups. We have further investigated the structure-activity relationship for GABA amides on the GABAAR by performing structural modifications to both the superagonist 2c and the agonist 6c. Synergism and [3H]muscimol binding experiments show that 2c binds to the same sites as GABA. Structural modification of 2c demonstrated that partial rigidification of the tether eliminated agonism and caused ligands to behave as weak competitive antagonists. We have also investigated the agonism of four ZAPA derivatives in 36Cl- uptake functional assay. Two of them are found to be as potent as GABA. In our studies of 1,4-benzodiazepines, our goal was to synthesize three different subtypes of quaternary 1,4-benzodiazepines by use of the memory of chirality (MOC) strategy. Disappointingly, most of the deprotonation/alkylations failed, due to various reasons. The failure of the reactions of (S)-alanine-derived tetrahydro-1,4-benzodiazepin-3-ones was probably due to either the unexpected side reactions or the steric hindrance of enolate alkylation. In the case of tetrahydro-1,4-benzodiazepin-2-ones, computational studies suggested that steric hindrance by both the benzo ring and N4-allyl group might retard deprotonation at C3 by bulky bases like KHMDS or LDA. Finally, (S)-serine-derived 1,4-benzodiazepin-2-ones and their elimination products (ï ¡-methylene benzodiazepines) were prepared. These proved unreactive towards deprotonation/alkylations and conjugate additions, respectively. The low reactivity of the ï ¡-methylene benzodiazepines towards nucleophiles was attributed to highly delocalized LUMOs that failed to direct nucleophiles to the ï ¢-carbons.Ph. D.
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Said, Najeeb Barrah. "The design and synthesis of non-peptide bradykinin B2 receptor antagonists." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285827.
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Canzoneri, Joshua Craig. "Interaction of small molecules with nucleic acid targets: from RNA secondary structure to the riobosome." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/45769.
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Nucleic acids have proven to be viable targets for small molecule drugs. While many examples of such drugs are detailed in the literature, only a select few have found practical use in a clinical setting. These currently employed nucleic acid targeting therapies suffer from either debilitating off-target side effects or succumb to a resistance mechanism of the target. The need for new small molecules that target nucleic acids is evident. However, designing a novel drug to bind to DNA or RNA requires a detailed understanding of exactly what binding environments each nucleic acid presents. In an effort to broaden this knowledge, the work presented in this thesis details the binding location and affinity of known and novel nucleic acid binding small molecules with targets ranging from simple RNA secondary structure all the way to the complex structure of ribosomal RNA. Specifically, it is shown that the anthracycline class of antineoplastics prefer to bind at or near mismatch base pairs in both physiologically relevant iron responsive element RNA hairpin constructs as well as DNA hairpin constructs presenting mismatched base pairs. Also characterized in this thesis is a novel class of topoisomerase II / histone deacetylase inhibitor conjugates that display a unique affinity for DNA over RNA. Finally, the novel class of macrolide-peptide conjugates, known as peptolides, are shown to retain potent translation inhibition of the prokaryotic ribosome. The binding pocket of the peptolides, including a crevice previously unreachable by macrolides that extends away from the peptidyl transferase center toward the subunit interface, is confirmed in detail via chemical footprinting of the 70S ribosome. Overall, the identification of a novel binding site for the anthracycline class of drugs and the characterization of the two novel drug designs presented in this thesis will undoubtedly aid in the effort to design and discover new molecules that aim for nucleic acid targets. For example, the anthracycline derivative topoisomerase II / histone deacetylase inhibitor conjugates, with their differential mode of nucleic acid binding, may prove to have a unique side effect profile in a therapeutic application. The peptolide compounds also have the potential to be applied as novel antibiotics as they bind to an area of the prokaryotic ribosome unrelated to known macrolide resistance mutations. Furthermore, as a result of the observation of this thesis work that some peptolides also posses eukaryotic translation inhibition capabilities, they could prove to be useful in preventing the growth of rapidly proliferating eukaryotic cells such as plasmodium, leishmania, or tumor cells. Additionally, different head groups could be utilized in creating new peptolides; for example, an oxazolidinone antibiotic could be employed to sample a different binding area of the ribosome.
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Wheeler, Graham Mark. "Adaptive designs for phase I dose-escalation studies." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708029.
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Chu, Yunhan. "Development of methods for de novo design of functional drugs and catalyst compounds." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for kjemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-14836.
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Alumasa, John N. "New insights on the structure-function principles and design of quinoline antimalarial drugs." Connect to Electronic Thesis (CONTENTdm), 2010. http://worldcat.org/oclc/642829236/viewonline.
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