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Synthesis and antidiabetic evaluation of some new coumarin coupled 4-thiazolidinone derivatives

A series of new 4-thiazolidinone derivatives were synthesized by reacting various coumarinyl schiff bases with thioglycollic acid. The intermediate coumarinyl schiff bases were synthesized by reacting 4-hydroxyl coumarin with various substituted anilines in alcohol medium. All the newly synthesized compounds were characterized on the basis of IR, 1H NMR and mass spectral data. All the newly synthesized compounds were evaluated for in-vitro antidiabetic activity by alpha-glucosidase inhibition assay. Most of the synthesised compounds showed good antidiabetic activity.

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Functional chemical groups that may likely become a source for the synthesis of novel central nervous system (CNS) acting drugs

Introduction: Central Nervous System (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identify functional chemical groups that may serve as lead molecules for synthesis of compounds that may have CNS activity. Methods: The search revealed that heterocycles that have heteroatoms such as nitrogen (N), sulphur (S) and oxygen (O) form the largest class of organic compounds. They replace carbon in a benzene ring to form pyridine. Compounds with furan, thiophene, pyrrole, pyridine, azole, imidazole, indole, purine, pyrimidine, esters, carboxylic acid, aldehyde, pyrylium, pyrone, pyrodine, barbituric acid, barbiturate, quinoline, quinolone, isoquinolone, coumarin, alkylpyridine, picoline, piperidine, diazine, carboxamide, flavonoid glycoside, oxindole, aminophenol, benzimidazole, benzoxazole, benzothiazole, and chromone chemical groups among others may have CNS effects ranging from depression passing through euphoria to convulsion. Results and Conclusion: Examples of the compounds with the functional groups include but not limited to coal tar, pyridostigmine, pralidoxime, quinine, mefloquine, pyrilamine, pyronaridine, ciprofloxacin and piroxicam. A number of them can undergo keto-enol tautomerism. Chiral amines may be used for derivation of chiral carboxylic acids which are components of tautomers. Some tautomers may cause parkinsonism and Stevens Johnson syndrome.

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Synthesis of a series of thiazolidinone derivatives and evaluation of their antimicrobial properties

A series of thiazolidinone derivatives with various aromatic aldehyde substitution were synthesized and characterized by physical (TLC and M.P.) and spectral data (IR, NMR and MASS). They were evaluated for antimicrobial potential against Gram positive Staphylococcus aureus, Bacillus subtilis, gram-negative Escherichia coli, Pseudomonas aeuroginosa, Shigella and fungi Candida albicans and Aspergillus niger. The initial screening using zones of inhibition at 50 mul concentration revealed that they are moderately active against the tested strains.

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A concise synthesis of mono- and polysubstituted and diversely N-function-alized isoindolinones and isoquinolones

A variety of differently substituted and diversely N-(sul-fanyl) hydroxyalkyl functionalized isoindolinones and isoquinolones have been obtained by anionic cyclization of cyclic bromobenzyl or bromophenethylcarbamates and thiocarbamates. Thieme Stuttgart.

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Synthesis and antimicrobial activity evaluation of the pyrrole-derived heterocycles bearing two functionalities

Background: The pyrrole ring is widely spread and incorporated into the structures of many naturally occurring compounds e.g. heme, chlorophyll, vitamin B12 and the bile pigments. Pyrrolnitrin and pyoluteorin are naturally occurring pyrroles which have antibiotic activity, and the methyl ester of 4-methylpyrrole-2-carboxylic acid is an insect pheromone. Moreover, the highly successful cholesterol lowering drug Lipitor is a poly substituted pyrrole derivative. Methods: Some novel pyrrole derivatives bearing other heterocyclic rings at positions-2 and -3 were synthesized and their antimicrobial activities were studied. Results: A series of novel pyrrolinthione, thiazolidinone, thiazolone, tetrazole, sulphonamides derivatives have been synthesized through a facile strategy and screened for antimicrobial activities, some of the prepared compounds exhibited high antibacterial and antifungal activities compared with the standard drugs. Conclusion: These compounds provided the impetus for most of the early work on the synthesis and reactions of pyrroles and still a very active of research. Many such explorations are anticipated in near future.

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Thiazolidin-4-one derivatives on human lung fibroblast shows oxygen free radical scavenging activity

The antioxidants are proving crucial tools in the exploration of oxidant stress-related diabetic pathologies and despite the noticeable prospective merit of the safety and efficacy of antioxidant supplementation in any future treatment remains to be conventional. The development of innovative methods for the synthesis of five-member heterocyclic compounds is an ever-expanding area in bioorganic and medicinal chemistry. Specifically, those containing the thiazolidinedione ring have been expansively used as key building blocks for synthesizing various drugs. In present study we endeavor to display a more chemically versatile and diverse thiazolidin-4-one derivatives as a suitable pharmacophore for antioxidant activity. Antioxidant activity was evaluated by using both enzymatic and non-enzymatic activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) on cell lines and free radical scavenging activity by DPPH (1, 1-diphenyl-2-picryl-hydrazil) assay method and ferric reducing antioxidant power (FRAP) assays. Finally, all tested compounds exhibited a talented antioxidant activity. In addition, all the synthesized derivatives showed non-toxic effects against a diseased human lung fibroblast (COPD), HCC7231 (TACC CCL-96). In prospect study, the movement of the compounds may be manipulated by optimizing a lead molecule by introducing un-saturation or heterocyclic ring at C5 of thiazolidinediones. The outcomes of such studies may be positive for the clinical applications in humans and may open up a new therapeutic avenue.

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Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors

BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited good antitumor effects in an MM.1S xenograft model by oral administration. Encouraged by its high potency and interesting scaffold, we performed further lead optimization to generate a novel potent series of bromodomain and extra-terminal (BET) inhibitors with a (1,2,4-triazol-5-yl)-3,4-dihydroquinoxalin-2(1H)-one structure. Among them, compound 19 was found to have the best balance of activity, stability, and antitumor efficacy. After confirming its low brain penetration, we conducted comprehensive preclinical studies, including a multiple-species pharmacokinetics profile, extensive cellular mechanism studies, hERG assay, and in vivo antitumor growth effect testing, and we found that compound 19 is a potential BET protein drug candidate for the treatment of cancer.

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Rad51/BRCA2 disruptors inhibit homologous recombination and synergize with olaparib in pancreatic cancer cells

Olaparib is a PARP inhibitor (PARPi). For patients bearing BRCA1 or BRCA2 mutations, olaparib is approved to treat ovarian cancer and in clinical trials to treat breast and pancreatic cancers. In BRCA2-defective patients, PARPi inhibits DNA single-strand break repair, while BRCA2 mutations hamper double-strand break repair. Recently, we identified a series of triazole derivatives that mimic BRCA2 mutations by disrupting the Rad51-BRCA2 interaction and thus double-strand break repair. Here, we have computationally designed, synthesized, and tested over 40 novel derivatives. Additionally, we designed and conducted novel biological assays to characterize how they disrupt the Rad51-BRCA2 interaction and inhibit double-strand break repair. These compounds synergized with olaparib to target pancreatic cancer cells with functional BRCA2. This supports the idea that small organic molecules can mimic genetic mutations to improve the profile of anticancer drugs for precision medicine. Moreover, this paradigm could be exploited in other genetic pathways to discover innovative anticancer targets and drug candidates.

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Archives for Chemistry Experiments of 2682-49-7

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Enhanced Proapoptotic Effects of Water Dispersed Complexes of 4-Thiazolidinone-Based Chemotherapeutics with a PEG-Containing Polymeric Nanocarrier

Aim: To study whether water formulation of the complex of 4-thiazolidinone derivatives with a PEG-containing polymeric nanocarrier enhances their pro-apoptotic action towards rat glioma C6 cells. Methods: Mechanisms of antineoplastic effects of 4-thiazolidinone derivatives were investigated in vitro with rat glioma C6 cells. Cell nativity, cell cycling pattern, and Annexin V expression were evaluated and DNA damage was estimated by DNA comet analysis. A novel water-based formulation of 4-thiazolidinone derivatives complexed with a polymeric nanocarrier was utilized for enhancing pro-apoptotic action towards C6 cells. Results: The studied 4-thiazolidinone derivatives use apoptosis mechanisms for killing rat glioma C6 cells, as confirmed by FACS analysis of these cells in pre-G1 stage, the appearance of Annexin V positive C6 cells, and an increased number of DNA comets of higher classes. Complexation of the studied compounds with a PEG-containing polymeric nanocarrier significantly increased pro-apoptotic effects in rat glioma C6 cells measured by all methods mentioned above. Conclusion: Complexation of 4-thiazolidinone derivatives with a PEG-containing polymeric nanocarrier provided them with water solubility and enhanced pro-apoptotic effects in rat glioma C6 cells.

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Design, synthesis and evaluation of Coumarin-Phenylthiazole conjugates as cholinesterase inhibitors

In this paper, we report the design, synthesis, in-silico, and in-vitro evaluations of a series of coumarin-phenylthiazole conjugates to inhibit cholinesterase enzymes. The coumarin and phenylthiazole derivatives have been synthesized separately, and further combined through covalent amine bond linkage. The synthesized compounds showed more inhibition towards BuChE than AChE, where 4-(3-bromophenyl)-1,3-thiazol-2-amine (7i) exhibited the strongest inhibition against BuChE with an IC50 value of 3.54 muM. For the conjugates, 3-[2-[4-(3-nitrophenyl)thiazol-2-ylamino]acetyl]chromen-2-one (8j) exhibited strongest inhibition with an IC50 value of 46.47 muM. The better inhibition activities towards BuChE are also shown by 3-bromo and 2-fluoro derivatives. It was also observed that the substitution at 3-position, on phenylthiazole moiety produced better results against BuChE than 4-substituted counterparts.

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