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Muñoz-Gómez, J. L., E. Monteagudo, V. Lloveras, T. Parella, J. Veciana, and J. Vidal-Gancedo. "A benzyl alcohol derivative of the BDPA radical for fast dissolution dynamic nuclear polarization NMR spectroscopy." Organic & Biomolecular Chemistry 13, no. 9 (2015): 2689–93. http://dx.doi.org/10.1039/c4ob02356k.
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Shormanov, V. K., N. G. Pogosyan, S. Yu Garmonov, and V. A. Omelchenko. "Application of gas chromatography for determination of 2-amino-4,6-dinitrophenol and evaluation of its stability in biological material." Uchenye Zapiski Kazanskogo Universiteta Seriya Estestvennye Nauki 167, no. 1 (2025): 53–65. https://doi.org/10.26907/2542-064x.2025.1.53-65.
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2-Amino-4,6-dinitrophenol (2-A-4,6-DNP), or picramic acid, is widely used as an intermediate in organic synthesis, a dye in hair coloring products, an agricultural fungicide, and an explosive. Similar to other related compounds (2,4,6-trinitrophenol (2,4,6-TNF) and N-methyl-N,2,4,6-tetranitroaniline), of which it is a metabolite, 2-A-4,6-DNP is toxic to humans and animals. However, certain aspects of its detection in toxicological screening remain poorly understood. In this study, a mixture of acetone and acetonitrile in equal amounts was identified as the most effective extractant for 2-A-4,6-DNP. The application of gas chromatography–mass spectrometry (GC–MS) for detecting 2-A-4,6-DNP in the biological material extracts was analyzed and justified. The proposed method, based on the indirect determination of 2-A-4,6-DNP through O-acetyl derivative quantification, was employed to assess its stability in the biolo- gical material. 2-A-4,6-DNP was found to be detectable in the biological medium within 25 (storage temperature 18–22 °C) to 45 (storage temperature 1–3 °C) days after the contamination.
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Albu, Paul Constantin, Szidonia-Katalin Tanczos, Andreea Ferencz (Dinu), et al. "pH and Design on n–Alkyl Alcohol Bulk Liquid Membranes for Improving Phenol Derivative Transport and Separation." Membranes 12, no. 4 (2022): 365. http://dx.doi.org/10.3390/membranes12040365.
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Regardless of the type of liquid membrane (LM) (Bulk Liquid Membranes (BLM), Supported Liquid Membranes (SLM) or Emulsion Liquid Membranes (ELM)), transport and separation of chemical species are conditioned by the operational (OP) and constructive design parameters (DP) of the permeation module. In the present study, the pH of the aqueous source phase (SP) and receiving phase (RP) of the proposed membrane system were selected as operational parameters. The mode of contacting the phases was chosen as the convective transport generator. The experiments used BLM-type membranes with spheres in free rotation as film contact elements of the aqueous phases with the membrane. The target chemical species were selected in the range of phenol derivatives (PD), 4–nitrophenol (NP), 2,4–dichlorophenol (DCP) and 2,4–dinitrophenol (DNP), all being substances of technical-economic and environmental interest. Due to their acid character, they allow the evaluation of the influence of pH as a determining operational parameter of transport and separation through a membrane consisting of n–octanol or n–decanol (n–AlcM). The comparative study performed for the transport of 4–nitrophenol (NP) showed that the module based on spheres (Ms) was more performant than the one with phase dispersion under the form of droplets (Md). The sphere material influenced the transport of 4–nitrophenol (NP). The transport module with glass spheres (Gl) was superior to the one using copper spheres (Cu), but especially with the one with steel spheres (St). In all the studied cases, the sphere-based module (Ms) had superior transport results compared to the module with droplets (Md). The extraction efficiency (EE) and the transport of 2,4–dichlorophenol (DCP) and 2,4–dinitrophenol (DNP), studied in the module with glass spheres, showed that the two phenolic derivatives could be separated by adjusting the pH of the source phase. At the acidic pH of the source phase (pH = 2), the two derivatives were extracted with good results (EE > 90%), while for pH values ranging from 4 to 6, they could be separated, with DCP having doubled separation efficiency compared to DNP. At a pH of 8 in the source phase, the extraction efficiency halved for both phenolic compounds.
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Yan, Zhang, Wang Jun-Hui, Luo Jian-Ping, Zhang Qiang, and Lu Jie. "The Structure-Activity Relationship and Molecular Mechanism of Anti-tumor Polysaccharide Isolated from Dendrobium nobile Lindl." Current Topics in Nutraceutical Research 17, no. 2 (2018): 153–63. http://dx.doi.org/10.37290/ctnr2641-452x.17:153-163.
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In this study, structure-activity relationship and molecular mechanism of anti-tumor polysaccharide isolated from the stems of Dendrobium nobile Lindl. were investigated. The sulfate and enzymatic analysis were employed to modify polysaccharide DNP-W1A, a fraction of polysaccharide isolated from D. nobile. Nine sulfated derivative fragments (S1–S9) and three fragments after enzymatic digestion (PE1, PE2 and PE3) were obtained using chloro-sulfonic acid and enzymatic methods, respectively. The activities experiment demonstrated that S1–S9, PE1, PE2 and PE3 showed significant anti-tumor activities in a dose-dependent manner (P < 0.05) in vitro. Annexin-FITC/PI results indicated that PE2 promoted the apoptosis of HepG2 cells at the highest rate of 19.3% compared with other fragments. Also, PE2 significantly increased the gene expression levels of Bax, Caspase-3 and Caspase-9 and suppressed the gene expression of Bcl-2 (P < 0.01). Meanwhile, HepG2 cells treated with polysaccharide resulted in suppressed P-AKT expression, and PE2 induced the lowest protein level of P-AKT compared with other fragments. The results concluded that polysaccharide DNP-W1A and its derivatives induced HepG2 cells apoptosis by up-regulating the gene expressions of Bax, Bcl-2, Caspase-3 and Caspase-9 and inhibiting the PI3K/AKT signaling pathway.
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Berd, David, Takami Sato, Henry C. Maguire, John Kairys, and Michael J. Mastrangelo. "Immunopharmacologic Analysis of an Autologous, Hapten-Modified Human Melanoma Vaccine." Journal of Clinical Oncology 22, no. 3 (2004): 403–15. http://dx.doi.org/10.1200/jco.2004.06.043.
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Purpose We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up. Patients and Methods Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guérin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials. Results The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P < .001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P < .001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program. Conclusion This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.
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Knight, C. G. "A quenched fluorescent substrate for thimet peptidase containing a new fluorescent amino acid, DL-2-amino-3-(7-methoxy-4-coumaryl)propionic acid." Biochemical Journal 274, no. 1 (1991): 45–48. http://dx.doi.org/10.1042/bj2740045.
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DL-2-Amino-3-(7-methoxy-4-coumaryl)propionic acid, a new fluorescent amino acid (abbreviated to Amp), has been synthesized to provide an alternative to tryptophan in quenched fluorescent peptide substrates for peptidases. The model compound Ac-DL-Amp-NH2 was intensely fluorescent with an excitation maximum at 328 nm and an emission maximum at 392 nm. Fmoc (fluoren-9-ylmethoxycarbonyl)-DL-Amp was made to allow the solid-phase synthesis of Amp-containing peptides by the Fmoc-polyamide method. The peptide derivative Dnp (2,4-dinitrophenyl)-Pro-Leu-Gly-Pro-DL-Amp-D-Lys was cleaved by thimet peptidase at the Leu-Gly bond, with a 20-fold enhancement of fluorescence. The value of kcat./Km for thimet peptidase was 6.7 x 10(5) M-1.s-1, compared with the value of 2.4 x 10(5) M-1.s-1 for the tryptophan-containing analogue, Dnp-Pro-Leu-Gly-Pro-Trp-D-Lys.
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Barrett, A. J., C. G. Knight, M. A. Brown, and U. Tisljar. "A continuous fluorimetric assay for clostridial collagenase and Pz-peptidase activity." Biochemical Journal 260, no. 1 (1989): 259–63. http://dx.doi.org/10.1042/bj2600259.
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The peptide derivative N alpha-(2,4-dinitrophenyl)-L-prolyl-L-leucyl-glycyl-L-prolyl-L-tryptophanyl-D- lysine (Dnp-Pro-Leu-Gly-Pro-Trp-D-Lys) has been found to be a convenient substrate for the assay of clostridial collagenase and Pz-peptidase. The substrate shows a 25-fold enhancement of fluorescence (gamma ex. 283 nm, lambda em. 350 nm) following hydrolysis of the Leu2-Gly3 peptide bond. The value of Km for clostridial collagenase was 17 microM. The substrate for the first time makes possible continuous fluorimetric assays for Pz-peptidase and clostridial collagenase.
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Li, Dongmi, Panpan Lv, Xiao-Wen Han, Zhilei Jia, Min Zheng, and Hai-Tao Feng. "A Highly Efficient Fluorescent Sensor Based on AIEgen for Detection of Nitrophenolic Explosives." Molecules 28, no. 1 (2022): 181. http://dx.doi.org/10.3390/molecules28010181.
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The detection of nitrophenolic explosives is important in counterterrorism and environmental protection, but it is still a challenge to identify the nitroaromatic compounds among those with a similar structure. Herein, a simple tetraphenylethene (TPE) derivative with aggregation-induced emission (AIE) characteristics was synthesized and used as a fluorescent sensor for the detection of nitrophenolic explosives (2, 4, 6-trinitrophenol, TNP and 2, 4-dinitrophenol, DNP) in water solution and in a solid state with a high selectivity. Meanwhile, it was found that only hydroxyl containing nitrophenolic explosives caused obvious fluorescence quenching. The sensing mechanism was investigated by using fluorescence titration and 1H NMR spectra. This simple AIE-active probe can potentially be applied to the construction of portable detection devices for explosives.
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Vissinga, Christine, Kelly Hensley, and Jacqueline Kirchner. "GPR34 is not required for mast cell degranulation induced by IgE or lysophosphatidyl-L-serine (36.1)." Journal of Immunology 182, no. 1_Supplement (2009): 36.1. http://dx.doi.org/10.4049/jimmunol.182.supp.36.1.
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Abstract Mast cells play an important role in allergic inflammation. Upon activation by cross-linking of FcεRI, they rapidly release granule-associated chemical mediators and secrete cytokines, fatty acids and lipids which mediate allergic inflammation. GPR34 is a GPCR expressed on mast cells and has been proposed to be a receptor for lysophosphatidylserine (lysoPS), a phospholipid derivative which can potentiate antigen-induced mast cell degranulation (BBRC 341: 1078, 2006). To determine if GPR34 is involved in mast cell response, we generated GPR34-/- mice and evaluated mast cell function in vitro and in vivo. Bone marrow-derived mast cells from GPR34+/+ and GPR34-/- mice exhibited similar responses, as measured by beta-hexosaminidase release, to IgE cross-linking or lysoPS stimulation. We evaluated the role of GPR34 in vivo using a passive cutaneous anaphylaxis model induced by crosslinking of FcεRI on mast cells. Mast cells in GPR34+/+ and GPR34-/- mice were activated by SC injection of anti-DNP IgE mAb followed by IV administration of DNP-BSA and Evans blue dye 24 hours later. Activation resulted in vascular permeability which was measured as the amount of dye influx. In this model, the mast cell response was unaffected by GPR34 gene deficiency. Together, our results indicate that GPR34 is not required for the mast cell response to IgE crosslinking in vitro or in vivo and that GPR34 is not a receptor for lysoPS.
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Shakibaie, Mohammad Reza, Balu Parnab Kapadnis, Pershant Dhakephalker, and Balu Ananda Chopade. "Removal of silver from photographic wastewater effluent using Acinetobacter baumannii BL54." Canadian Journal of Microbiology 45, no. 12 (1999): 995–1000. http://dx.doi.org/10.1139/w99-077.
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Acinetobacter baumannii BL54, a silver (Ag) resistant micro-organism was isolated from clinical samples collected at the Armed Forces Medical College hospital in Pune, India. The strain BL54 removed a high quantity of silver (2.85 mg/g biomass) from photographic wastewater effluent. Treatment of the cells with 10 mM EDTA or agitating the culture did not affect the removal process, while altering pH of the wastewater or pre-treating the cells with 0.5 mM 2,4-dinitrophenol (DNP), 20 μM N,N'-dicyclohexylcarbodiimide (DCC), 25 μg/mL cefotaxime, and polymyxin-B resulted in considerable decrease in removal of silver by the organism. Dead cells, or a Ags plasmid-cured derivative (BL54.1) removed little silver, which was mainly surface bound. The results, compared with accumulation of Ag by a sensitive culture of Escherichia coli K12 J53.2, suggest that A. baumannii BL54 has good potential for bioremediation of silver from photographic wastewater effluents. Key words: Acinetobacter, silver resistance, silver removal.
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Dust, Julian M., and Richard A. Manderville. "Carbon versus oxygen nucleophilic selectivity in the reaction of the aryloxide ions, 2,6- and 3,5-di-tert-butylphenoxide, with the 2-[(nitro)\dn6 xaryl]-4,6-dinitrobenzotriazole 1-oxide series of super-electrophiles. Stereoelectronic factors on C-7 Meisenheimer complex formation versus C-1' SNAr displacement." Canadian Journal of Chemistry 76, no. 6 (1998): 662–71. http://dx.doi.org/10.1139/v98-028.
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The 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides (1, Pi-DNBT (x = 3); 2, DNP-DNBT (x = 2); 3, NP-DNBT (x = 1)) are electron-deficient nitro-substituted heteroaromatic substrates that possess two sites for nucleophilic attachment: C-7 and C-1'. Generally, attack at the super-electrophilic C-7 site yields spectroscopically observable anionic sigma -bonded adducts, whereas attack at C-1' leads to displacement products in an overall process of nucleophilic aromatic substitution (SNAr). To gain an understanding of the factors affecting C-1' versus C-7 attack by potentially ambident aryloxide (C- and O-)nucleophiles, we have monitored the reactions of 1-3 with 2,6-di-tert-butylphenoxide (2,6-ArO-) and 3,5-di-tert-butylphenoxide (3,5-ArO-) using 400 MHz 1H NMR spectroscopy (deuterated dimethyl sulfoxide solvent at ambient temperature). The results indicate that 2,6-ArO- acts only as a C-nucleophile with O-attack precluded, presumably by the sterically demanding tert-butyl groups flanking the O-nucleophilic centre. Although 2,6-ArO- reacts preferentially at C-7 of 1-3, the biphenyl derivative that arises from C-1' attack is also observed with 1, the first time that C-nucleophilic attack has been seen at this electrophilic site. In contrast, 3,5-ArO- acts only as an O-nucleophile, also as a consequence of the steric hindrance to the C-4 position; this aryloxide reacts entirely at C-1' of Pi-DNBT but also exclusively at C-7 of 3. However, with DNP-DNBT, 2, both the C-7 O-adduct and C-1' displacement products are noted; attack at C-1' is dominant. The selectivity (C-7 versus C-1') found in these reactions is discussed with emphasis given to stereoelectronic factors that may stabilize the putative C-1' O-adducts.Key words: aryloxides, super-electrophiles, Meisenheimer complexes, 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides.
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Schwack, Wolfgang, Tatjana Zeisler, and Constanze Stiefel. "Determination of Dialkyl Phosphates as Breakdown Products of Organophosphorus Insecticides in Fruit Juices by HPTLC with Fluorescence Detection." Journal of AOAC INTERNATIONAL 92, no. 3 (2009): 691–98. http://dx.doi.org/10.1093/jaoac/92.3.691.
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Abstract Dialkyl phosphates (DAP) are common degradation products of organophosphorus pesticides that are used as urinary biomarkers for human exposure. An HPTLC method was developed for the quantitative determination of DAP in fruit juices, i.e., dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP), diethyl phosphate (DEP), and diethyl thiophosphate (DETP). Dibutyl phosphate (DBP) was used as an internal standard. The method was based on precipitation of fruit acids in the presence of barium chloride and acetonitrile and liquidliquid extraction with acetonitrilediethyl ether. Extracted DAP were derivatized with 1-(bromoacetyl)pyrene (BAP), and the BAP derivatives separated on HPTLC amino plates with dichloromethane as the mobile phase. Densitometry was performed by measurement of fluorescence at 366/&gt;400 nm. The limit of quantification (LOQ) values were between 0.8 and 1.4 ng/zone. Fluorescence enhancement was achieved by dipping the plate into a paraffin oil solution, increasing the sensitivity and resulting in an LOQ of 0.50.6 ng/zone. Repeatabilities with relative standard deviations of 3.5 (n = 5, at 1520 ng/zone) and coefficients of correlation of 0.9999 were highly satisfactory for rapid trace analysis of DAP in the fruit juices by HPTLC. The mean recoveries from apple juice spiked at 0.5 mg/L were 74, 83, 70, and 57 for DMP, DEP, DMTP, and DETP, respectively. If an application volume of 5 L of apple juice extract was applied, the LOQ in apple juice was 300 g/L. However, this can be lowered by application of higher volumes (up to 50 L) or a more concentrated derivatization batch.
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Muñoz-Gómez, J. L., E. Monteagudo, V. Lloveras, T. Parella, J. Veciana, and J. Vidal-Gancedo. "Optimized polarization build-up times in dissolution DNP-NMR using a benzyl amino derivative of BDPA." RSC Advances 6, no. 32 (2016): 27077–82. http://dx.doi.org/10.1039/c6ra00635c.
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Prabhu, Anila, and R. K. Saxena. "Comparison of murine B-cell proliferative response to bacterial lipopolysaccharide and DNP derivative ofMycobacterium tuberculosis antigens." Journal of Biosciences 19, no. 1 (1994): 57–65. http://dx.doi.org/10.1007/bf02703468.
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MOHD., ALI, and SHARMA NlRMAL. "Characterisation of Chemical Constituents of Gliricidia meculata Leaves." Journal of Indian Chemical Society Vol. 74, Aug 1997 (1997): 658–59. https://doi.org/10.5281/zenodo.5895292.
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Faculty of Pharmacy, Jarnia Hamdard (Hamdard University), Hamdard Nagar, New Delhi-110 062 <em>Manuscript received 16 June 1994, revised 15 February 1996, accepted 24 June 1996</em> Characterisation of Chemical Constituents of Gliricidia meculata Leaves.
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Plitzner, Patrick, Andreas Müller, Anton Güntsch, et al. "The CDM Applied: Unit-Derivation, from Field Observations to DNA Sequences." Biodiversity Information Science and Standards 1 (August 16, 2017): e20366. https://doi.org/10.3897/tdwgproceedings.1.20366.
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Specimens form the falsifiable evidence used in plant systematics. Derivatives of specimens (including the specimen as the organism in the field) such as tissue and DNA samples play an increasing role in research. The EDIT Platform for Cybertaxonomy is a specialist's tool that allows to document and sustainably store all data that are used in the taxonomic work process, from field data to DNA sequences. The types of data stored can be very heterogeneous consisting of specimens, images, text data, primary data files, taxon assignments, etc. The EDIT Platform organizes the linking between such data by using a generic data model for representing the research process. Each step in the process is regarded as a derivation step and generates a derivative of the previous step. This could be a field unit having a specimen as its derivative or a specimen having a tissue sample as its derivative. Each derivation step also produces meta data storing who, when and how the derivation was done. The Platform's Common Data Model (CDM) and the applications build on the CDM library thus represent the first comprehensive implementation of the largely theoretical models developed in the late 1990ies (Berendsohn et al. 1999). In a pilot project research data about the genus <em>Campanula</em> (Kilian et al. 2015, FUB, BGBM 2012) was gathered and used to create a hierarchy of derivatives reaching from field data to DNA sequences. Additionally, the open source library for multiple sequence alignments LibrAlign (Stöver and Müller 2015) was used to integrate an alignment editor into the EDIT platform that allows to generate consensus sequences as derivatives of DNA sequences. The persistent storage of each link in the derivation process and the degree of detail on how the data and meta data are stored will speed up the research process, ease the reproducibility of research results and enhance sustainability of collections.
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Lehrer, R. I., D. Szklarek, A. Barton, T. Ganz, K. J. Hamann, and G. J. Gleich. "Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein." Journal of Immunology 142, no. 12 (1989): 4428–34. http://dx.doi.org/10.4049/jimmunol.142.12.4428.
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Abstract We examined the bactericidal activity of two proteins that are abundant in the cytoplasmic granules of human eosinophils, major basic protein (MBP) and eosinophil cationic protein (ECP). Unlike the human neutrophil's peptide defensins, both MBP and ECP killed stationary phase Staphylococcus aureus 502A in a simple nutrient-free buffer solution. Although MBP also killed Escherichia coli ML-35 with considerable efficacy under these experimental conditions, the in vitro activity of ECP against E. coli was considerably enhanced if mid-logarithmic phase bacteria replaced stationary phase organisms or if the assay medium was enriched with trypticase soy broth. The antibacterial activity of both eosinophil proteins was modulated by incubation time, protein concentration, temperature and pH. A pBR322-transformed derivative of E. coli ML-35 was used to examine the effects of ECP and MBP on integrity of the bacterial inner membrane (IM) and outer membrane. Although both MBP and ECP caused outer and inner membrane permeabilization when nutrients were present, only MBP was effective under nutrient-free conditions. Two proton ionophores (DNP and carbonyl cyanide m-chlorophenyl hydrazone) protected E. coli from the bactericidal effects of ECP but not from MBP. These findings establish that MBP and ECP have bactericidal properties and suggest that these proteins kill E. coli by similar but nonidentical mechanisms marked by an attack on the target cell's membranes. In view of evidence that high concentrations of ECP and MBP exist in cytoplasmic granules whose contents are translocated to phagocytic vacuoles, we suggest that MBP and ECP contribute to the eosinophil's ability to kill ingested bacteria.
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Zhang, Haigang, Chengji Zhao, and Hui Na. "Enhanced Biodegradation of Phthalic Acid Esters’ Derivatives by Plasticizer-Degrading Bacteria (Burkholderia cepacia, Archaeoglobus fulgidus, Pseudomonas aeruginosa) Using a Correction 3D-QSAR Model." International Journal of Environmental Research and Public Health 17, no. 15 (2020): 5299. http://dx.doi.org/10.3390/ijerph17155299.
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A phthalic acid ester’s (PAEs) comprehensive biodegradability three-dimensional structure-activity relationship (3D-QSAR) model was established, to design environmentally friendly PAE derivatives, which could be simultaneously degraded by plasticizer-degrading bacteria, such as Burkholderia cepacia, Archaeoglobus fulgidus, and Pseudomonas aeruginosa. Only three derivatives of diethyl phthalate (DEP (DEP-27, DEP-28 and DEP-29)) were suited for their functionality and environmental friendliness, which had an improved stability in the environment and improved the characteristics (bio-toxicity, bioaccumulation, persistence, and long-range migration) of the persistent organic pollutants (POPs). The simulation inference of the microbial degradation path before and after DEP modification and the calculation of the reaction energy barrier exhibited the energy barrier for degradation being reduced after DEP modification and was consistent with the increased ratio of comprehensive biodegradability. This confirmed the effectiveness of the comparative molecular similarity index analysis (CoMSIA) model of the PAE’s comprehensive biodegradability. In addition, a molecular dynamics simulation revealed that the binding of the DEP-29 derivative with the three plasticizer-degradation enzymes increased significantly. DEP-29 could be used as a methyl phthalate derivative that synergistically degrades with microplastics, providing directional selection and theoretical designing for plasticizer replacement.
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Martynov, Artur, Boris Farber, and Alexander Katz. "Phosphodiesterase Inhibition and Immunotropic Activity of Dipyridamole Dynamic Derivatives." Current Issues in Molecular Biology 47, no. 4 (2025): 214. https://doi.org/10.3390/cimb47040214.
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Introduction. Many pharmacological properties of dipyridamole (DIP) are associated with its ability to inhibit phosphodiesterases (PDEs). Actually, DIP has interesting properties like antiviral for influenza, SARS-2 COVID-19, and herpesviruses. Our research aimed to design and synthesize the dynamic combinatorial DIP derivatives with more pronounced inhibiting properties in relation to PDE and to carry out the HPLC analysis of the resulting combinatorial derivatives of DIP. This study is aimed at investigating the effect of the dynamic derivative of dipyridamole (DDD) on intestinal dysbiosis syndrome in mice caused by streptomycin against the background of cyclophosphamide-induced cellular immunodeficiency. Materials and methods. For the synthesis of a dynamic combinatorial derivative of dipyridamole, we used a molecular dynamic method for drug design and combinatorial acylation of dipyridamole by succinic and acetic anhydride in different molar ranges of acylation agents. Combinatorial derivatives were analyzed using gradient HPLC with a UV detector. Also, derivatives established the inhibition ability for phosphodiesterase by the spectrophotometric method. Also, we used an in vivo mouse model with immunodeficiency caused by cyclophosphamide for pharmacological study. Results and discussion. Molecular modeling suggests that 18 different dipyridamole derivatives can self-assemble into a stable supramolecular structure with lower total energy. Specific combinatorial molar ratios of the synthesis components were necessary to create a new supramolecular compound with enhanced pharmacological properties. The inhibition of phosphodiesterase in such a dynamic combinatorial derivative already appeared at a concentration of 0.05 μM. In mice with colitis caused by streptomycin treatment, the administration of DDD per os resulted in an antidiarrheal effect and prevention of the animals’ weight loss. Given the cyclophosphamide-induced immunosuppression and streptomycin-associated diarrhea, immunity was completely restored only under the action of DDD. Conclusions. The most effective dipyridamole derivative for phosphodiesterase inhibition was formed only if the number of different derivatives in solution was maximum and consisted of all 18 molecules. With other quantities of modifiers, there was no qualitative change in the inhibitory activity of the combinatorial mixture against phosphodiesterase. According to all parameters, DDD has been proven to be more effective than the pure dipyridamole reference product.
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Soltan, Marwa, Uly Sumarni, Chalid Assaf, Peter Langer, Ulrich Reidel, and Jürgen Eberle. "Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells." International Journal of Molecular Sciences 20, no. 5 (2019): 1158. http://dx.doi.org/10.3390/ijms20051158.
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Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative.
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Rucins, Martins, Pavels Dimitrijevs, Klavs Pajuste, et al. "Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines." Pharmaceutics 11, no. 3 (2019): 115. http://dx.doi.org/10.3390/pharmaceutics11030115.
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The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 µM (compound 11) to 43.3 µM (compound 6). The tested 4-(N-alkylpyridinium)-1,4-DHP derivatives were able to quench the fluorescence of the binary 1,6-diphenyl-1,3,5-hexatriene (DPH)—1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) system, demonstrating hydrophobic interactions of 1,4-DHPs with phospholipids. Thus, 4-(N-dodecylpyridinium)-1,4-DHP derivative 3 quenched the fluorescence of the DPH–DPPC system more efficiently than the other 4-(N-alkylpyridinium)-1,4-DHP derivatives. Likewise the compound 3, also 4-(N-dodecylpyridinium)-1,4-DHP derivative 9 interacted with the phospholipids. Moreover, we have established that increasing the length of the alkyl chain at the quaternised nitrogen of the 4-(N-alkylpyridinium)-1,4-DHP molecule or the introduction of propargyl moieties in the 1,4-DHP molecule significantly influences the cytotoxicity on HT-1080 (human fibrosarcoma) and MH-22A (mouse hepatocarcinoma) cell lines, as well as the estimated basal cytotoxicity. Additionally, it was demonstrated that the toxicity of the 4-(N-alkylpyridinium)-1,4-DHP derivatives on the Gram-positive and Gram-negative bacteria species and eukaryotic microorganism depended on the presence of the alkyl chain length at the N-alkyl pyridinium moiety, as well as the number of propargyl groups. These lipid-like compounds may be proposed for the further development of drug formulations to be used in cancer treatment.
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Gómez, Iban, Ester Viteri, Jessica Montero, Mile Djurdjevic, and Gerhard Huber. "The Determination of Dendrite Coherency Point Characteristics Using Three New Methods for Aluminum Alloys." Applied Sciences 8, no. 8 (2018): 1236. http://dx.doi.org/10.3390/app8081236.
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The aim of this work is to give an overview of existing methods and to introduce three new methods for the determination of the Dendrite Coherency Point (DCP) for AlSi10Mg alloys, as well as to compare the acquired values of DCP based on a thermal analysis and on the analysis of cooling curves working with only one thermocouple. Additionally, the impact of alloying and contaminant elements on the DCP will be also studied. The first two proposed methods employ the higher order derivatives of the cooling curves. The DCP was determined as the crossing point of the second and third derivative curves plotted versus time (method 1) or that of the temperature (method 2) with the zero line just after the maximum liquidus temperature. The third proposed method is based on the determination of the crossing point of the third solid fraction derivative curve with the zero line, corresponding to a minimum of the second derivative. A Taguchi design for the experiments was developed to study the DCP values in the AlSi10Mg alloy. The DCP temperature values of the test alloys were compared with the DCP temperatures predicted by the previous methods and the influence of the major and minor alloying elements and contaminants over the DCP. The new processes obtained a correlation factor r2 from 0.954 and 0.979 and a standard deviation from 1.84 to 2.6 °C. The obtained correlation values are higher or similar than those obtained using previous methods with an easier way to define the DCP, allowing for a better automation of the accuracy of DCP determination. The use of derivative curves plotted versus temperature employed in the last two proposed methods, where the test samples did not have an influence over the registration curves, is proposed to have a better accuracy than those of the previously described methods.
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Li, Yaoguo, and Douglas W. Oldenburg. "Incorporating geological dip information into geophysical inversions." GEOPHYSICS 65, no. 1 (2000): 148–57. http://dx.doi.org/10.1190/1.1444705.
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Geological bodies are often linear structures that have well‐defined strike direction and dip angle. We develop a new model objective function that allows this important information to be incorporated into geophysical inversions. A rotation matrix is applied to the horizontal and vertical derivatives of the model so that the derivative in an arbitrary direction is obtained. A model objective function that measures the flatness with respect to the rotated derivatives favors models that have elongated features with the specified strike and dip angle. Formulations for both 2-D and 3-D cases are presented, and they are illustrated using examples from dc resistivity and induced polarization (IP) problems. Synthetic and field examples show that an inversion carried out using known dip information produces a model that has higher resolution and provides a better representation of the true structure.
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Ammendola, Serena, Valerio Secli, Francesca Pacello, et al. "Salmonella Typhimurium and Pseudomonas aeruginosa Respond Differently to the Fe Chelator Deferiprone and to Some Novel Deferiprone Derivatives." International Journal of Molecular Sciences 22, no. 19 (2021): 10217. http://dx.doi.org/10.3390/ijms221910217.
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The ability to obtain Fe is critical for pathogens to multiply in their host. For this reason, there is significant interest in the identification of compounds that might interfere with Fe management in bacteria. Here we have tested the response of two Gram-negative pathogens, Salmonella enterica serovar Typhimurium (STM) and Pseudomonas aeruginosa (PAO1), to deferiprone (DFP), a chelating agent already in use for the treatment of thalassemia, and to some DFP derivatives designed to increase its lipophilicity. Our results indicate that DFP effectively inhibits the growth of PAO1, but not STM. Similarly, Fe-dependent genes of the two microorganisms respond differently to this agent. DFP is, however, capable of inhibiting an STM strain unable to synthesize enterochelin, while its effect on PAO1 is not related to the capability to produce siderophores. Using a fluorescent derivative of DFP we have shown that this chelator can penetrate very quickly into PAO1, but not into STM, suggesting that a selective receptor exists in Pseudomonas. Some of the tested derivatives have shown a greater ability to interfere with Fe homeostasis in STM compared to DFP, whereas most, although not all, were less active than DFP against PAO1, possibly due to interference of the added chemical tails with the receptor-mediated recognition process. The results reported in this work indicate that DFP can have different effects on distinct microorganisms, but that it is possible to obtain derivatives with a broader antimicrobial action.
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Mishra, Abhinav Prasoon, Ankit Bajpai, and Awani Kumar Rai. "1,4-Dihydropyridine: A Dependable Heterocyclic Ring with the Promising and the Most Anticipable Therapeutic Effects." Mini-Reviews in Medicinal Chemistry 19, no. 15 (2019): 1219–54. http://dx.doi.org/10.2174/1389557519666190425184749.
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: Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.
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Wang, Yu, Fan Bo Wang, Li Bo Du, and Yu Guang Lv. "Synthesis and Study of Fluorescent Probe Molecules Based on Rhodamine Class B Derivatives." Key Engineering Materials 881 (April 2021): 117–22. http://dx.doi.org/10.4028/www.scientific.net/kem.881.117.
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In this paper, a fluorescent probe based on a rhodamine spirolactam ring was designed and synthesized. Rhodamine derivatives not only have excellent chemical and optical-physical properties, but also the "OFF-ON" characteristic of the rhodamine spiroamide ring allows specific recognition and response to metal ions. In this paper, Rh-DCP, a rhodamine B derivative with a spirolactam ring, was synthesized by the Schiff base reaction and the effects of pH, time and temperature on this probe were tested.
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Golemis, E. A., and R. Brent. "Fused protein domains inhibit DNA binding by LexA." Molecular and Cellular Biology 12, no. 7 (1992): 3006–14. http://dx.doi.org/10.1128/mcb.12.7.3006-3014.1992.
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Many studies of transcription activation employ fusions of activation domains to DNA binding domains derived from the bacterial repressor LexA and the yeast activator GAL4. Such studies often implicitly assume that DNA binding by the chimeric proteins is equivalent to that of the protein donating the DNA binding moiety. To directly investigate this issue, we compared operator binding by a series of LexA-derivative proteins to operator binding by native LexA, by using both in vivo and in vitro assays. We show that operator binding by many proteins such as LexA-Myc, LexA-Fos, and LexA-Bicoid is severely impaired, while binding of other LexA-derivative proteins, such as those that carry bacterially encoded acidic sequences ("acid blobs"), is not. Our results also show that DNA binding by LexA derivatives that contain the LexA carboxy-terminal dimerization domain (amino acids 88 to 202) is considerably stronger than binding by fusions that lack it and that heterologous dimerization motifs cannot substitute for the LexA88-202 function. These results suggest the need to reevaluate some previous studies of activation that employed LexA derivatives and modifications to recent experimental approaches that use LexA and GAL4 derivatives to detect and study protein-protein interactions.
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Golemis, E. A., and R. Brent. "Fused protein domains inhibit DNA binding by LexA." Molecular and Cellular Biology 12, no. 7 (1992): 3006–14. http://dx.doi.org/10.1128/mcb.12.7.3006.
Full textAbstract:
Many studies of transcription activation employ fusions of activation domains to DNA binding domains derived from the bacterial repressor LexA and the yeast activator GAL4. Such studies often implicitly assume that DNA binding by the chimeric proteins is equivalent to that of the protein donating the DNA binding moiety. To directly investigate this issue, we compared operator binding by a series of LexA-derivative proteins to operator binding by native LexA, by using both in vivo and in vitro assays. We show that operator binding by many proteins such as LexA-Myc, LexA-Fos, and LexA-Bicoid is severely impaired, while binding of other LexA-derivative proteins, such as those that carry bacterially encoded acidic sequences ("acid blobs"), is not. Our results also show that DNA binding by LexA derivatives that contain the LexA carboxy-terminal dimerization domain (amino acids 88 to 202) is considerably stronger than binding by fusions that lack it and that heterologous dimerization motifs cannot substitute for the LexA88-202 function. These results suggest the need to reevaluate some previous studies of activation that employed LexA derivatives and modifications to recent experimental approaches that use LexA and GAL4 derivatives to detect and study protein-protein interactions.
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Kirikovich, Svetlana S., Evgeniy V. Levites, Anastasia S. Proskurina, et al. "The Molecular Aspects of Functional Activity of Macrophage-Activating Factor GcMAF." International Journal of Molecular Sciences 24, no. 24 (2023): 17396. http://dx.doi.org/10.3390/ijms242417396.
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Group-specific component macrophage-activating factor (GcMAF) is the vitamin D3-binding protein (DBP) deglycosylated at Thr420. The protein is believed to exhibit a wide range of therapeutic properties associated with the activation of macrophagal immunity. An original method for GcMAF production, DBP conversion to GcMAF, and the analysis of the activating potency of GcMAF was developed in this study. Data unveiling the molecular causes of macrophage activation were obtained. GcMAF was found to interact with three CLEC10A derivatives having molecular weights of 29 kDa, 63 kDa, and 65 kDa. GcMAF interacts with high-molecular-weight derivatives via Ca2+-dependent receptor engagement. Binding to the 65 kDa or 63 kDa derivative determines the pro- and anti-inflammatory direction of cytokine mRNA expression: 65 kDa—pro-inflammatory (TNF-α, IL-1β) and 63 kDa—anti-inflammatory (TGF-β, IL-10). No Ca2+ ions are required for the interaction with the canonical 29 kDa CLEC10A. Both forms, DBP protein and GcMAF, bind to the 29 kDa CLEC10A. This interaction is characterized by the stochastic mRNA synthesis of the analyzed cytokines. Ex vivo experiments have demonstrated that when there is an excess of GcMAF ligand, CLEC10A forms aggregate, and the mRNA synthesis of analyzed cytokines is inhibited. A schematic diagram of the presumable mechanism of interaction between the CLEC10A derivatives and GcMAF is provided. The principles and elements of standardizing the GcMAF preparation are elaborated.
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Król, M., T. Tański, G. Matula, P. Snopiński, and A. E. Tomiczek. "Analysis of Crystallisation Process of Cast Magnesium Alloys Based on Thermal Derivative Analysis / Analiza Procesu Krystalizacji Odlewniczych Stopów Magnezu W Oparciu O Analizę Termicznoderywacyjną." Archives of Metallurgy and Materials 60, no. 4 (2015): 2993–3000. http://dx.doi.org/10.1515/amm-2015-0478.
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The paper presents the results of the crystallisation process of cast magnesium alloys based on the thermal-derivation analysis. The effects of aluminium content and cooling rate on the characteristic parameters of the evaluation of magnesium dendrites during solidification at different cooling rates were investigated by thermal-derivative analysis (TDA). Dendrite coherency point (DCP) is defined with a new approach based on the second derivative cooling curve. Solidification behaviour was evaluated via one thermocouple thermal analysis method. Microstructural evaluations were characterised by light microscope, X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. This research revealed that utilisation of d2T/dt2 versus the time curve methodology allows for analysis of the dendrite coherency point.
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Correia, Daniela M., Erlantz Lizundia, Rafaela M. Meira, Mikel Rincón-Iglesias, and Senentxu Lanceros-Méndez. "Cellulose Nanocrystal and Water-Soluble Cellulose Derivative Based Electromechanical Bending Actuators." Materials 13, no. 10 (2020): 2294. http://dx.doi.org/10.3390/ma13102294.
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This study reports a versatile method for the development of cellulose nanocrystals (CNCs) and water-soluble cellulose derivatives (methyl cellulose (MC), hydroxypropyl cellulose (HPC), and sodium carboxymethyl cellulose (NaCMC)) films comprising the ionic liquid (IL) 2-hydroxy-ethyl-trimethylammonium dihydrogen phosphate ([Ch][DHP]) for actuator fabrication. The influence of the IL content on the morphology and physico–chemical properties of free-standing composite films was evaluated. Independently of the cellulose derivative, the ductility of the films increases upon [Ch][DHP] incorporation to yield elongation at break values of nearly 15%. An increase on the electrical conductivity as a result of the IL incorporation into cellulosic matrices is found. The actuator performance of composites was evaluated, NaCMC/[Ch][DHP] showing the maximum displacement along the x-axis of 9 mm at 8 Vpp. Based on the obtained high electromechanical actuation performance, together with their simple processability and renewable nature, the materials fabricated here represent a step forward in the development of sustainable soft actuators of high practical relevance.
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Khunnawutmanotham, Nisachon, Watthanachai Jumpathong, Chatchakorn Eurtivong, Nitirat Chimnoi, and Supanna Techasakul. "Synthesis, cytotoxicity evaluation, and molecular modeling studies of 2,N10-substituted acridones as DNA-intercalating agents." Journal of Chemical Research 44, no. 7-8 (2020): 410–25. http://dx.doi.org/10.1177/1747519820902674.
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Acridine-based compounds possess anticancer activities by intercalating to DNA. Although they have chemotherapeutic potential, acridine-based compounds are not used to treat cancer. In this study, 2, N10-acridone derivatives are designed and synthesized based on acridone, a ketone derivative of acridine. Herein, acridone is functionalized with alkyl side chains containing terminal nitrogen-based moieties at the N10-position and substituted at the C2-position. The products are evaluated for in vitro cytotoxicity against four cancer cell lines: Molt-3, HepG2, A549, and HuCCA-1. The derivative bearing two butyl piperidine side chains at the C2- and N10-positions is the most active, with IC50 values ranging from 2.96 to 9.46 µM. Molecular modeling studies supported the binding of the derivatives to DNA by intercalation, thereby confirming the observed cytotoxic effects.
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Zhang, Haigang, Chengji Zhao, and Hui Na. "PAEs Derivatives’ Design for Insulation: Integrated In-Silico Methods, Functional Assessment and Environmentally Friendly Molecular Modification." International Journal of Environmental Research and Public Health 19, no. 6 (2022): 3232. http://dx.doi.org/10.3390/ijerph19063232.
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As a common substance in production and life, phthalic acid esters (PAEs), the main component of plastics, have brought more and more serious problems to the environment. This study normalized the insulation, toxicity, and bioconcentration data of 13 PAEs to eliminate the dimensional coefficients of each index, and then used the comprehensive index method to calculate the comprehensive effect value of PAEs with three properties. The comprehensive effect value was used as the data source to construct the 3D-QSAR model of PAE molecular comprehensive effect. The DAP was selected as the target molecule, the distribution of each force field in the three-dimensional equipotential map was analyzed, and 30 molecular modification schemes were created. The constructed single-effect models of insulation, toxicity, and bioconcentration of PAEs and the scoring function module of DS software were used to evaluate the stability and environmental friendliness of PAE derivative molecules. Four PAE derivatives were screened for increased comprehensive effects, enhanced insulation, and reduced toxicity and bioconcentration. By calculating the binding energy of the target molecule and the derivative molecule with the degrading enzyme under different applied electric fields, it was found that the binding energy of DAP-1-NO2-2-CH2C6H5 decreases more than DAP does when there is an applied electric field, indicating that the degradation ability of degrading enzymes on PAE derivative molecules is reduced, which indirectly proves that the insulation is enhanced. The innovation of this paper lies in the insulation, toxicity, and bioenrichment data of PAEs being processed by mathematical method for the first time, and PAEs with high insulation, low toxicity, and low bioconcentration were designed by building a comprehensive model.
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Greenhalgh, S. A., B. Zhou, M. Greenhalgh, L. Marescot, and T. Wiese. "Explicit expressions for the Fréchet derivatives in 3D anisotropic resistivity inversion." GEOPHYSICS 74, no. 3 (2009): F31—F43. http://dx.doi.org/10.1190/1.3111114.
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We have developed explicit expressions for the Fréchet derivatives or sensitivity functions in resistivity imaging of a heterogeneous and fully anisotropic earth. The formulation involves the Green’s functions and their gradients, and it is developed from a formal perturbation analysis and by means of a numerical (finite-element) method. A critical factor in the equations is the derivative of the electrical conductivity tensor with respect to the principal conductivity values and the angles defining the axes of symmetry. The Fréchet derivative expressions were derived for the 2.5D and 3D problems using constant-point and constant-block model parameterizations. Special cases such as an isotropic earth and tilted transversely isotropic (TTI) media emerge from the general solutions. Numerical examples were investigated for various sensitivities as functions of dip angle and strike of the plane of stratification in uniform TTI media.
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Ozolins, Reinis, Mara Plotniece, Karlis Pajuste, et al. "1,1′-{[3,5-Bis((dodecyloxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis[4-(anthracen-9-yl)pyridin-1-ium] Dibromide." Molbank 2022, no. 3 (2022): M1438. http://dx.doi.org/10.3390/m1438.
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A synthesis of a cationic moiety and fluorescent moieties containing amphiphilic 1,4-dihydropyridine (1,4-DHP) derivatives was performed starting with the Hantzsch-type cyclization of dodecyl acetoacetate, phenylaldehyde and ammonium acetate. Bromination of the 2,6-dimethyl groups of a parent 1,4-DHP compound, followed by nucleophilic substitution of bromine with 4-(anthracen-9-yl)pyridine, produced the desired 1,1′-{[3,5-bis((dodecyloxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis[4-(anthracen-9-yl)pyridin-1-ium] dibromide. The obtained target compound was fully characterized by the IR, 1H NMR, 13C NMR and HRMS data. Studies of the self-assembling properties and characterization of the nanoparticles obtained by the ethanol injection method were performed using dynamic light scattering (DLS) measurements. DLS measurement data showed that 1,1′-{[3,5-bis((dodecyloxycarbonyl)-4-phenyl-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis[4-(anthracen-9-yl)pyridin-1-ium] dibromide produced liposomes that had average diameters of 200 nm when the samples were freshly prepared, and 140 nm after 7 days or 1 month storage. The PDI values of the samples were approximately 0.50 and their zeta-potential values were approximately 41 mV when the samples were freshly prepared, and 33 mV after storage. The obtained nanoparticles were stored at room temperature for one month and remained stable during that period. The mean molecular area of the cationic 1,4-DHP-anthracene hybrid 4 was 118 Å2, while the mean molecular area of the cationic 1,4-DHP 5 without anthracene substituents was only 83 Å2. The photoluminescence quantum yield (PLQY) value for the EtOH solution of the 1,4-DHP derivative 4 was 10.8%, but for the 1,4-DHP derivative 5 it was only 1.8%. These types of compounds could be used as synthetic lipids in the further development of prospective theranostic delivery systems.
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Li, Cheng, Chunjing Liu, Rongzhen Li, Yue Liu, Jianzhi Xie, and Bowen Li. "Biodegradation of Dibutyl Phthalate by the New Strain Acinetobacter baumannii DP-2." Toxics 10, no. 9 (2022): 532. http://dx.doi.org/10.3390/toxics10090532.
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Optimizing the culture conditions of DBP degradation by bacteria and investigating its biodegradation pathways have a great importance to develop effective PAEs pollution control strategies. In this study, we investigated the cultivation condition optimization, degradation kinetics, and degradation pathways of a newly isolated dibutyl phthalate (DBP) degradation strain, which was isolated from activated sludge and identified as Acinetobacter baumannii DP-2 via morphological observation, biochemical identification, and 16S rDNA sequence analysis. The degradation conditions were optimized based on the results of single-factor experiments and response surface optimization experiments. The DBP degradation rate of Acinetobacter baumannii DP-2 reached up to 98.89% when the inoculation amount was 17.14%, the DBP concentration was 9.81 mg·L−1 and the NaCl concentration was 5 g·L−1. The GC-MS analysis results indicated that the intermediate metabolites of Acinetobacter baumannii DP-2 mainly consisted of DMP, MBP, PA, and benzoic acid derivatives, which confirmed the degradation pathway from DBP to PA under aerobic pathway and then to BA under anaerobic pathway. In summary, Acinetobacter baumannii DP-2 shows great potential for the degradation of DBP in contaminated soils.
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Ramakrishna, C., and G. V. Subbareddy. "Synthesis Docking Studies and Antitubercular Activity of Ofloxacin Scaffold using Blanc Reaction." Asian Journal of Chemistry 34, no. 3 (2022): 644–50. http://dx.doi.org/10.14233/ajchem.2022.23584.
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Synthesis, molecular docking and characterization of ofloxacin derivatives and in vitro evaluation for their antitubercular action were carried out. Synthesis ofloxacin derivatives viz. O+TRI, O+MEL, O+NAP, O+SUL, O+METF, O+IBU, O+ASP, O+DNP, O+SSA, O+PH, O+MC (where TRI = trimethoprim, MEL = meloxicam, NAP = naproxen, SUL = sulfamethoxazole, METF = metformin, IBU = ibuprofen, ASP = aspirin, DNP = 2,4-dinitrophenyl hydrazine, SSA = 5-sulpho salicylic acid, PH = phenyl hydrazine, MC = 7-hydroxy-4-methyl coumarin) were carried using Blanc reaction and purified by using of ethanol by recrystallization. The reaction products consist of methylene group linkage between two moieties and the molecules were characterized by analytical methods TLC, solubility, melting point, spectroscopic methods (FT-IR, mass and 1H NMR, 13C NMR). In silico methods were adopted for synthetic derivatives by Autodock vina software. Determined physico-chemical parameters (in silico studies) and docking studies have been performed using protein (5BS8) with designed ligands, binding energy scores were noted for different derivatives. Derivatives O+TRI, O+NAP shown good activity at 0.8 μg/mL. In docking studies, all the compounds shown promising results when compared to standard drugs.
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Zeynep Ceylan and eyda Deniz Ayd n, Zeynep Ceylan and eyda Deniz Ayd n. "Investigation of the Effect of Substituent Species/Positions and Numbers on Removal of Toxicity from Chloro and Nitro Phenol Compounds with Fenton and Fenton-like Processes." Journal of the chemical society of pakistan 42, no. 5 (2020): 639. http://dx.doi.org/10.52568/000676/jcsp/42.05.2020.
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Phenol derivatives containing substutient are used intensely in industry and their presence in surface and waste water is a problem requiring urgent solution due to their tendency for bioaccumulation, cancerogenic effects, high toxicity and weak biodegradability. In this study, the degradability and toxicity of chlorinated phenols 2-CP, 2,4-DCP and 4-CP and nitrated phenols 2-NP, 2,4-DNP and 4-NP were investigated. These phenols are included on the priority toxic pollutant list within the scope of clean water regulations according to both the US EPA-2014 and the European Union (2455/2001/CE) and form serious threats to public health and aqueous ecosystems. The degradability of chloro and nitro phenols was researched by applying the Fenton/Fenton-like processes (under optimal conditions) and measuring the model pollutant concentrations, COD and TOC parameters. The effects of substituent type/position and number were determined with toxicity measurements using Vibrio fischeri bacteria (DIN/EN/ISO 11348-2). Statistical analysis was performed in detail for both Fenton/Fenton-like processes (T test) and toxicology measurement results (One-Way ANOVA) for the model pollutants (Pandlt;0.05). In the first stage of the study, model pollutant removal of 95-100%, COD removal of 64-85% / 60-77% and TOC removal efficiency of 52-65% and 40-61% were achieved respectively with Fenton and Fenton-like processes. In the second stage of the study, the results of toxicity measurements of the pollutants performed before processing found EC50(mg/L) and toxic unit values (TU) were 8.10-12.34 for 2-CP, 2.24-44.67 for 2,4-DCP, 1.20-83.33 for 4-CP, 13.43-7.44 for 2-NP, 8.92-11.21 for 2,4-DNP, and 4.77-20.9 for 4-NP, respectively. After processing, the EC50/EC20 and TU values were determined to fall to unobservable levels. According to the order obtained with toxicity measurements of 4-CP andgt; 2,4-DCP andgt; 4-NP andgt; 2-CP andgt; 2,4-DNP andgt; 2-NP, the chlor substituent had higher toxic effect compared to nitro. As the substituent numbers increase the toxicity increased; however, para position was identified to be more toxic compared to other positions. The reason for the 4 (para) position being more toxic than the 2,4 (ortho-para) position is thought to be due to the chlor or nitro linked to the 2 or ortho position binding to the OH group of phenol with a 5- and 6-member H-bridge in cis position forming a ring, which leads to inactivity.
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Nazarova, Anastasia, Pavel Padnya, Arthur Khannanov, Aleksandra Khabibrakhmanova, Pavel Zelenikhin, and Ivan Stoikov. "Towards Protection of Nucleic Acids from Herbicide Attack: Self-Assembly of Betaines Based on Pillar[5]arene with Glyphosate and DNA." International Journal of Molecular Sciences 24, no. 9 (2023): 8357. http://dx.doi.org/10.3390/ijms24098357.
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Herbicides are one of the main parts of pesticides used today. Due to the high efficiency and widespread use of glyphosate-based herbicides, the search for substances reducing their genotoxicity is an important interdisciplinary task. One possible approach for solving the problem of herbicide toxicity is to use compounds that can protect DNA from damage by glyphosate derivatives. For the first time, a method for developing DNA-protecting measures against glyphosate isopropylamine salt (GIS) damage was presented and realized, based on low-toxicity water-soluble pillar[5]arene derivatives. Two- and three-component systems based on pillar[5]arene derivatives, GIS, and model DNA from salmon sperm, as well as their cytotoxicity, were studied. The synthesized pillar[5]arene derivatives do not interact with GIS, while GIS is able to bind DNA from salmon sperm with lgKa = 4.92. The pillar[5]arene betaine derivative containing fragments of L-phenylalanine and the ester derivative with diglycine fragments bind DNA with lgKa = 5.24 and lgKa = 4.88, respectively. The study of the associates (pillar[5]arene-DNA) with GIS showed that the interaction of GIS with DNA is inhibited only by the betaine pillar[5]arene containing fragments of L-Phe (lgKa = 3.60). This study has shown a possible application of betaine pillar[5]arene derivatives for nucleic acid protection according to its competitive binding with biomacromolecules.
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Wang, Xiaoming, Ghazala Akram, Maasoomah Sadaf, Hajra Mariyam та Muhammad Abbas. "Soliton Solution of the Peyrard–Bishop–Dauxois Model of DNA Dynamics with M-Truncated and β-Fractional Derivatives Using Kudryashov’s R Function Method". Fractal and Fractional 6, № 10 (2022): 616. http://dx.doi.org/10.3390/fractalfract6100616.
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In this paper, the Peyrard–Bishop–Dauxois model of DNA dynamics is discussed along with the fractional effects of the M-truncated derivative and β-derivative. The Kudryashov’s R method was applied to the model in order to obtain a solitary wave solution. The obtained solution is explained graphically and the fractional effects of the β and M-truncated derivatives are also shown for a better understanding of the model.
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Cooper, Gordon R. J. "The automatic determination of the location, depth, and dip of contacts from aeromagnetic data." GEOPHYSICS 79, no. 3 (2014): J35—J41. http://dx.doi.org/10.1190/geo2013-0181.1.
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A simple new method (termed the contact-depth method) for the determination of the depth, location, and dip of contacts from pole reduced magnetic data was evaluated. The depth was obtained by computing the horizontal derivative of the tangent of the tilt angle of the magnetic field over the contact. Although it is based upon the tilt-depth method, it does not require the distance between contour lines to be measured, and it additionally allows the dip of the contact to be estimated from the gradient of the depth estimates. The horizontal location of the contact is that of the zero value of the tilt angle. The method uses second- and third-order derivatives of the magnetic field to obtain the parameters of the contact, so it is sensitive to noise. When tested on synthetic data and on aeromagnetic data from southern Africa, the method gave plausible results.
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Aljohani, Ahmed K. B., Sanadelaslam S. A. El-Hddad, Marwa Alsulaimany, et al. "Design, nanogel synthesis, anti-proliferative activity and in silico ADMET profile of pyrazoles and pyrimidines as topo-II inhibitors and DNA intercalators." RSC Advances 15, no. 13 (2025): 10037–48. https://doi.org/10.1039/d5ra00166h.
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Vlasova, Kseniya Yu, Petr Ostroverkhov, Daria Vedenyapina, et al. "Liposomal Form of 2,4-Dinitrophenol Lipophilic Derivatives as a Promising Therapeutic Agent for ATP Synthesis Inhibition." Nanomaterials 12, no. 13 (2022): 2162. http://dx.doi.org/10.3390/nano12132162.
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Mitochondrial uncoupler 2,4-dinitrophenol (2,4-DNP) is a promising antidiabetic and antiobesity agent. Its clinical use is limited by a narrow dynamic range and accumulation in non-target sensitive organs, which results in whole-body toxicity. A liposomal formulation could enable the mentioned drawbacks to be overcome and simplify the liver-targeted delivery and sustained release of 2,4-DNP. We synthesized 2,4-DNP esters with carboxylic acids of various lipophilic degrees using carboxylic acid chloride and then loaded them into liposomes. We demonstrated the effective increase in the entrapment of 2,4-DNP into liposomes when esters were used. Here, we examined the dependence of the sustained release of 2,4-DNP from liposomes on the lipid composition and LogPoct of the ester. We posit that the optimal chain length of the ester should be close to the palmitic acid and the lipid membrane should be composed of phospholipids with a certain phase transition point depending on the desired release rate. The increased effect of the ATP synthesis inhibition of the liposomal forms of caproic and palmitic acid esters compared to free molecules in liver hepatocytes was demonstrated. The liposomes’ stability could well be responsible for this result. This work demonstrates promising possibilities for the liver-targeted delivery of the 2,4-DNP esters with carboxylic acids loaded into liposomes for ATP synthesis inhibition.
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Nicolás, Álvaro, Julia G. Quero, Marta Barroso, Zoila Gándara, and Lourdes Gude. "DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative." Biology 13, no. 1 (2024): 60. http://dx.doi.org/10.3390/biology13010060.
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Four 1,10-phenanthroline derivatives (1–4) were synthesized as potential telomeric DNA binders, three substituted in their chains with thiosemicarbazones (TSCs) and one 4-phenylthiazole derivative. The compounds were characterized using NMR, HRMS, FTIR-spectroscopy and combustion elemental analysis. Quadruplex and dsDNA interactions were preliminarily studied, especially for neutral derivative 1, using FRET-based DNA melting assays, equilibrium dialysis (both competitive and non-competitive), circular dichroism and viscosity titrations. The TSC derivatives bind and stabilize the telomeric Tel22 quadruplex more efficiently than dsDNA, with an estimated 24-fold selectivity determined through equilibrium dialysis for compound 1. In addition, cytotoxic activity against various tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29) and two normal cell lines (HFF-1 and RWPE-1) was evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the compounds showed moderate cytotoxic properties, with the salts displaying lower IC50 values (30–80 μM), compared to the neutral TSC, except in PC-3 cells (IC50 (1) = 18 μM). However, the neutral derivative was the only compound that exhibited a modest selectivity in the case of prostate cells (tumor PC-3 versus healthy RWPE-1). Cell cycle analysis and Annexin V/PI assays revealed that the compounds can produce cell death by apoptosis, an effect that has proven to be similar to that demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties, such as PhenDC3 and PhenQE8.
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Sapkota, Kamal Raj, Shilpi Kumari, Zeba Alam, and Md Serajul Haque Faizi. "Synthesis, and Structural Characterization of (E)-1-(4-((2-(2,4-Dinitrophenyl) hydrazono) methyl)phenyl) piperidine: A Combined Spectroscopic and Computational Study." Bhairahawa Campus Journal 7, no. 1 (2024): 41–55. https://doi.org/10.3126/bhairahawacj.v7i1.79948.
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This study Hydrazine-based piperidine derivatives are widely recognized for their significant roles in pharmaceutical development and material science research. In this context, the present study aimed to synthesize a novel hydrazone derivative to explore its structural and electronic features. This study presents the synthesis and structural characterization of (E)-1-(4-((2-(2,4-Dinitrophenyl)hydrazono)methyl)phenyl)piperidine) (DHP). The compound was obtained through a condensation reaction between 4-(piperidin-1-yl) benzaldehyde and (2,4-dinitrophenyl) hydrazine, achieving an 88% yield. Its structure was confirmed using ¹H NMR, ¹³C NMR, FT-IR, and UV-Vis spectroscopy. Molecular electrostatic potential (MEP) analysis highlighted regions of charge distribution, with electronegative zones concentrated around nitro (-NO₂) groups and electropositive areas near the hydrazone linkage. The UV-Vis spectrum exhibited a peak at 406 nm, attributed to π–π* transitions and intramolecular charge transfer. The results validate the successful synthesis and structural integrity of DHP, underscoring its significance in organic synthesis, photophysical investigations, and material science.
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Weissberg, Avi, Tamar Shamai Yamin, Avital Shifrovitch, Adi Tzadok, Merav Blanca, and Moran Madmon. "Enhancing the Detection and Identification Sensitivity of Organophosphorus Pesticide-Related Phenols via Derivatization and LC-ESI-MS/MS: A Straightforward Approach to Identify the Specific Pesticide Involved in Exposure." Environments 12, no. 6 (2025): 193. https://doi.org/10.3390/environments12060193.
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Organophosphorus (OP) pesticides are a class of chemicals that are extensively used worldwide. The exposure to and use of organophosphates can be assessed by analyzing their metabolites and degradation products, such as dialkyl phosphate (DAP), dialkyl thiophosphate (DATP), and dialkyl dithiophosphate (DADTP). However, since these metabolites/hydrolysis products can result from the metabolism or breakdown of several organophosphorus pesticide families, they serve as nonspecific biomarkers and do not indicate the specific pesticide involved in exposure. In an earlier study, chemical derivatization using N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAX-B) was described to improve the signal intensity of numerous organophosphorus (OP) acids in liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS) analysis. In the present study, CAX-B was employed to derivatize a set of seven phenolic compounds corresponding to the complementary portion of OP pesticides. The derivatization process using CAX-B was performed in acetonitrile with potassium carbonate at 50 °C for 30 min. LC-Orbitrap-ESI-MS/MS was used to analyze the resulting phenol derivatives and their fragmentation patterns were studied. Notably, the derivatized phenols were markedly more sensitive than the underivatized phenols when LC-ESI-MS/MS was used in MRM technique, without being affected by the sample matrix (soil or plant extracts). This derivatization technique aids in identifying OP pesticides, offers insights into their subfamily, and pinpoints a specific compound through the analysis of corresponding phenol derivative.
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Gayathri Somasundaram and Kumaran Rajendran. "Photo Physical Properties of Sugar Derivatives with ICT Dye." International Research Journal on Advanced Engineering and Management (IRJAEM) 2, no. 10 (2024): 3104–10. http://dx.doi.org/10.47392/irjaem.2024.0458.
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Photo physical techniques were employed to study hydrogen-bonding self-assemblies forming sugar derivatives interaction with 4-dicyanomethylene 2, 6-dimethyl-4H-pyran (DDP) dye in aqueous medium. Hydrogen-bonding self-assemblies were investigated by addition of sugar derivatives to DDP dye which is an Intramolecular Charge Transfer (ICT) based fluorescent probe, results in a fluorescence enhancement accompanied with a shift towards the red region. The coexistence of DDP dye with sugar derivatives signifies the presence of heterogeneous micro environment of DDP dye surrounded by varying proportion of the solute and water molecules around the dye moiety. sugar derivatives influence the excited state characteristics of DDP dye resulting in the formation and promotion of different distinguishable micro environment. The hydrophobicity of sugar derivatives along with the hydrogen-bonding properties of sugar -water and sugar - sugar largely influence the photo physical nature of DDP dye is emphasized.
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Hesterberg, Rebecca S., and Pearlie K. Epling-Burnette. "Genetic Ablation of Cereblon (CRBN) Increases Long-Lived Memory T Cells." Blood 126, no. 23 (2015): 3440. http://dx.doi.org/10.1182/blood.v126.23.3440.3440.
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Background: Immunomodulatory drugs (IMiDs) consist of thalidomide and derivatives, pomalidomide and lenalidomide. IMiDs target the E3 ubiquitin ligase substrate receptor, cereblon (CRBN), which forms a complex with DDB1-Cul4A, to induce anti-proliferative effects in tumor cells and increase the activation of T cells. Using crbn deficient T-cells, we have shown that CRBN is a negative regulator of T cell activation in mice. Dynamic changes in the T-cell repertoire occur after thymic involution. With the reduction of thymic output with age, there is a loss of naïve T-cells in the peripheral blood, and the accumulation of a memory-like T-cell population that arises through homeostatic proliferation. In this study, we demonstrate the role of CRBN in peripheral homeostatic regulation during aging. Methods: In this study, C57BL6 crbn -/- mice were housed in pathogen-free conditions to limit foreign antigen exposure. Splenocytes were stained with T cell markers to define various memory populations from 3, 8, 10 and 13 month old crbn -/- and age-matched wild-type mice. Expression of CD8, CD44, CD127 (IL-7 receptor) and KLRG1 were determined by flow cytometry. CD44-CD127+ KLRG1- CD8+ T cells were considered naive in this analysis. Consistent with previous reports, CD44+ CD127+ KLRG1- T cells represent long-term memory T-cells while CD44+CD127-KLRG1+ T cells are effector memory cells. To better understand age-related changes in the thymus, the thymus was dissected and the absolute number of thymocytes was determined by trypan blue staining. Thymic subpopulations were defined using CD4 and CD8 as single positive, double positive, and double negative cells in 13 month old crbn -/- and WT mice. We further characterized double negative (DN) populations using CD44 and CD25 to define DN1, DN2, DN3, and DN4. Results: Splenocytes in 3 and 8 month old crbn -/- and WT mice have no significant differences in CD44+ memory cells, naïve cells (p=0.7850 and p=0.5061) or recently activated cells [CD69+ or CD25+]. Changes related to thymic involution in WT mice become evident at 10 months of age. Crbn -/- mice exhibit a similar percentage and absolute number of total memory cells (p=0.8194) at 10 months of age, as defined by CD44 expression. Evaluation of long-lived versus short-lived sub-populations of memory cells in these older mice showed that crbn deficiency is associated with significantly more CD44+ CD127+ KLRG1- CD8+ [long-lived] memory T cells compared to WT mice (p<0.001). Evaluation of the thymus revealed no difference in absolute numbers of thymocytes in younger mice. Moreover, crbn deficient mice have normal distribution of SP, DP, and DN populations, with only slight changes in DN1, DN2, DN3, and DN4 subpopulations. Absolute numbers of thymocytes, however, were significantly higher in the crbn -/- mice at 10 months of age compared to age-matched controls (p=0.0182). Conclusions: The fate of developing T cells is regulated by positive and negative selection in the thymus where the coordination and selection of self-tolerant repertoire is maintained. Age-related changes caused by thymic involution impacts the protective responses of these cells against foreign pathogens and tumor cells. Our data show that the genetic germline depletion of crbn leads to an increase in long-lived memory T cells in naturally aged animals. Universally in cancer patients, and especially in MDS, the lymphocyte compartment is characterized by premature age-related changes due possibly to reduction in lymphopoiesis at the stem cell level or due to chronic antigen stimulation. Given that the CD44+ CD127+ KLRG1- population is significantly higher in aged crbn -/- mice, these mice may be more resistant to viral infection and or development of malignancy. The mechanism responsible for this phenotypic difference could be due to cell intrinsic signaling or metabolic properties. However, a role for CRBN in thymic epithelial cells must also be considered given the use of germline deficient animals in this study. Taken together, we have demonstrated that ablation of crbn results in an increase in long-lived CD8+ T cells during aging, which suggests that targeting CRBN and/or treating with lenalidomide may functionally improve memory T cell capacity in the elderly. Disclosures No relevant conflicts of interest to declare.
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Merlin, J., A. N'Doye, T. Bouriez, and G. Dolivet. "Polyethylenimine derivatives as potent nonviral vectors for gene transfer." Drug News & Perspectives 15, no. 7 (2002): 445. http://dx.doi.org/10.1358/dnp.2002.15.7.840080.
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Kusuhara, Hiroyuki, Yong-Hae Han, Minoru Shimoda, Eiichi Kokue, Hiroshi Suzuki, and Yuichi Sugiyama. "Reduced folate derivatives are endogenous substrates for cMOAT in rats." American Journal of Physiology-Gastrointestinal and Liver Physiology 275, no. 4 (1998): G789—G796. http://dx.doi.org/10.1152/ajpgi.1998.275.4.g789.
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We examined the role of the canalicular multispecific organic anion transporter (cMOAT) in the biliary excretion of reduced folate derivatives in vivo and in vitro using normal [Sprague-Dawley rats (SDR)] and mutant [Eisai hyperbilirubinemic rats (EHBR)] rats whose cMOAT is hereditarily deficient. In vivo, the biliary excretion of endogenous tetrahydrofolate (H4PteGlu), 5-methyltetrahydrofolate (5-CH3-H4PteGlu), and 5,10-methylenetetrahydrofolate (5,10-CH2-H4PteGlu) in EHBR was reduced to 8.2%, 1.9%, and 5.5% of those in SDR, respectively, whereas that of 10-formyltetrahydrofolate (10-HCO-H4PteGlu) was detected only in SDR and not in EHBR. Bile drainage caused reduction of endogenous plasma folate concentrations in SDR but not in EHBR. In vitro, significant ATP-dependent uptake of3H-labeled 5-CH3-H4PteGlu into canalicular membrane vesicles was observed only in SDR. This ATP-dependent uptake was saturable with a Michaelis constant ( K m) value of 126 μM, which was comparable with its inhibitor constant ( K i) value of 121 μM for the ATP-dependent uptake of a typical cMOAT substrate, 2,4-dinitrophenyl- S-glutathione (DNP-SG). Vice versa, DNP-SG inhibited the uptake of 5-CH3-H4PteGlu with a K i of 35 μM, which was similar to its K m value. In addition, H4PteGlu and 5,10-CH2-H4PteGlu also inhibited the ATP-dependent uptake of DNP-SG. These results indicate that 5-CH3-H4PteGlu and other derivatives are transported via cMOAT. Therefore, reduced folate derivatives are the first endogenous substrates for cMOAT that do not contain glutathione, glucuronide, or sulfate moieties.