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Synthesis, characterization and antimicrobial screening of quinoline based quinazolinone-4-thiazolidinone heterocycles

In an attempt to find new pharmacologically active molecules, we report here the synthesis and in vitro antimicrobial activity of various 2-(2-chloro-6-methyl(3-quinolyl))-3-[2-(4-chlorophenyl)-4-oxo(3-hydroquinazolin-3-yl)]-5-[(aryl)methylene]-1,3-thiazolidin-4-ones. In vitro antimicrobial activity of the title compounds are screened against two Gram positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), two Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and three strains of fungi (Candida albicans, Aspergillus niger, Aspergillus clavatus) using broth micro dilution method. Some derivatives bearing chloro or hydroxy group exhibited very good antimicrobial activity.

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MODULATORS OF G-PROTEIN COUPLED RECEPTORS

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize or partially agonize or antagonize) glucagon?like peptide?1 receptor (“GLP?1R”) and/or the gastric inhibitory polypeptide receptor (“GIPR”). The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which modulation (e.g., agonism, partial agonism or antagonism) of GLP?1R and/or GIPR activities is benficial for the treatment or prevention of the underlying pathology and/or symptoms and/or progression of the disease, disorder, or condition. In some embodiments, the modulation results in an enhancment of (e.g., an increase in) existing levels (e.g., normal or below normal levels) of GLP?1R and/or GIPR activity (e.g., signaling). In some embodiments, the chemical entities described herein further modulate (e.g., attenuate, uncouple) -arrestin signaling relative to what is observed with the native ligand. This disclosure also features compositions as well as other methods of using and making the said chemical entities.

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Electrochemical Oxidative C(sp3)?H/N?H Cross-Coupling for N-Mannich Bases with Hydrogen Evolution

N-Mannich bases are an important structure in various functional molecules. A new protocol to synthesize N-Mannich bases was established through electrochemical external-oxidant-free C(sp3)?H/N?H cross-coupling with hydrogen evolution. Various N-methylanilines were explored in this transformation. Moreover, simple amides, heteroatom-containing amides, and succinimides were well tolerated in moderate-to-good yields. In addition, the electrochemical dehydrogenative C(sp3)?H/N?H cross-coupling could be scaled up to 5 mmol. By using triethyl phosphite as trapping agent, the phosphorylation product was detected. At the same time, kinetic isotope effect experiments showed that the cleavage of the C?H bond is the rate-limiting step.

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Nitroimidazoles: Part XVI – Some 1-Methyl-4-nitro-5-substituted Imidazoles

Treatment of 1-methyl-4-nitro-5-chloroimidazole (3) with 5-membered lactames, e.g. imidazolidinones, oxazolidinone and thiazolidinone affords N-imidazolyl derivatives (4a-d).Reaction of 3 with imidazole yields 4e; amino derivatives (4f-h) are similarly obtained. 2-Hydroxypyrazine, 4-hydroxyquinazoline and 3,4,5-trichlorophenol and 3 react to form O-derivatives (4i-k).Imidazole (11) is formed from 1-methyl-4-chloro-5-nitroimidazole (10).

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Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment

Selenium(Se)-containing compounds have attracted a growing interest as anticancer agents over recent decades, with mounting reports demonstrating their high efficacy and selectivity against cancer cells. Typically, Se compounds exert their cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis. However, the precise intracellular targets, signalling pathways affected and mechanisms of cell death engaged following treatment vary with the chemical properties of the selenocompound and its metabolites, as well as the cancer model that is used. Naturally occurring organic Se compounds, besides encompassing a significant antitumor activity with an apparent ability to prevent metastasis, also seem to have fewer side effects and less systemic effects as reported for many inorganic Se compounds. On this basis, many novel organoselenium compounds have also been synthesized and examined as potential chemotherapeutic agents. This review aims to summarize the most well studied natural and synthetic organoselenium compounds and provide the most recent developments in our understanding of the molecular mechanisms that underlie their potential anticancer effects.

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An update on chemical classes targeting ERK1/2 for the management of cancer

Cancer, still in the limelight due to its dreadful nature, shows overexpression of multiple signaling macromolecules leading to failure of many chemotherapeutic agents and acquired resistance to chemotherapy. These factors highlight the significance of shifting toward targeted therapy in cancer research. Recently, ERKs (ERK1 and 2) have been established as a promising target for the management of various types of solid tumors, due to their aberrant involvement in cell growth and progression. Several ERKs inhibitors have reached clinical trials for the management of cancer and their derivatives are being continuously reported with noteworthy anticancer effect. This review highlights the recent reports on various chemical classes involved in the development of ERKs inhibitors along with their in vitro and in vivo activity and structure-activity relationship profile.

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Synthesis, characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides

Background: A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8. Results: All the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 muM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC50 = 0.00005 and 0.00012 muM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC50 = 0.00615 muM/ml) taken as standard drug. Conclusion: The molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

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Synthesis, characterization and antimicrobial screening of some novel 5-(benzofuran-2-yl)-N?-(2-substituted-4-oxothiazolidin-3-YL)-1-phenyl-1hpyrazole- 3-carboxamide derivatives

A series of innovative 5-(benzofuran-2-yl)-N?-(2-substituted-4-oxothiazolidin-3-yl)-1-phenyl-1H-pyrazole-3- carboxamide (4a-i) derivatives were synthesized by cyclocondensation reaction of various carbohydrazones (3a-i) with thioglycolic acid in DMF. The intermediate N?-(benzylidene)-5-(benzofuran-2-yl)-1- phenyl-1H-pyrazole-3-carbohydrazides (3a-i) was obtained by condensation of 5-(benzofuran-2-yl)-1-phenyl-1Hpyrazole- 3-carbohydrazide (1) with various substituted aromatic aldehydes (2a-i) in ethanol. The structures of newly synthesized compounds (4a-i) were corroborated through elemental analysis and spectral studies like IR, 1H NMR, 13C NMR and Mass spectra. The compounds were screened for their in-vitro antibacterial activity against a panel of pathogenic microorganism including gram-negative strains E. coli, P. vulgaris and S. typhi and grampositive bacterial strain, S. aureus at diverse concentrations and the result of bioassay was compared with Chloramphenicol.

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So3h-functionalized zeolite-y as an efficient nanocatalyst for the synthesis of n-benzimidazole-2-aryl-4-thiazolidinones and tri-substituted imidazoles

Background: SO3H-functionalized zeolite-Y was prepared and used as a catalyst for the synthesis of 2-aryl-N-benzimidazole-4-thiazolidinones and tri-substituted imidazoles at ambient conditions. Objective: The goals of this catalytic method include excellent yields and high purity, inexpensive procedure and ease of product isolation, the use of nontoxic and heterogeneous acid catalyst, shorter reaction times and milder conditions. Materials and Methods: NMR spectra were recorded on Brucker spectrophotometer using Me4Si as internal standard. Mass spectra were recorded on an Agilent Technology 5975C VL MSD with tripe-axis detector. FT-IR spectra were obtained with KBr disc on a galaxy series FT-IR 5000 spectrometer. The surface morphology of nanostructures was analyzed by FE-SEM (EVO LS 10, Zeiss, Carl Zeiss, Germany). BET analysis were measured at 196 C by a Japan Belsorb II system after the samples were vacuum dried at 150C overnight. Results: The NSZ was characterized by FT-IR, FESEM, EDX, XRF, and BET. The catalytic activity of NSZ was investigated for synthesis of 1,3-tiazolidin-4-ones in H2O/Acetone at room temperature. Moreover, NSZ was used for synthesis of tri-substituted imidazoles at 60 C via solvent-free condensation. Different kinds of aromatic aldehydes were converted to the corresponding of products with good to excellent yields. Conclusion: Sulfonated zeolite-Y was as an efficient catalyst for the preparation of N-benzimidazole-2-aryl-1,3-thiazolidin-4-ones and 2,4,5-triaryl-1H-imidazoles. High reaction rates, elimination toxic solvent, simple experimental procedure and reusability of the catalyst are the important features of this protocol.

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Quinoxaline and quinoxaline-1,4-di-N-oxides: An emerging class of antimycobacterials

Tuberculosis (TB) is a highly dreaded, infectious, chronic, airborne disease affecting more than two million people all around the world, with more than eight million cases every calendar year. TB is the second leading infectious cause of death after HIV/AIDS. Over the past few decades, numerous efforts have been undertaken to develop new anti-TB agents. The current frontline therapy for TB consists of administering three or more different drugs (usually isoniazid, rifampin, pyrazinamide, and ethambutol) over an extended period of time. But these drugs will take 6?12 months to cure TB, along with many side effects; hence, there is an urgent need to explore new anti-TB agents. Quinoxaline derivatives are a class of compounds that show a spectrum of biological properties and the interest in these compounds is exponentially growing within the field of medicinal chemistry. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas. Since quinoxaline derivatives are regarded as a new class of effective anti-TB candidates, their 1,4-di-N-oxide analogues may show promising in vitro and in vivo anti-TB activities and might be able to prevent the drug resistance to a certain extent. Therefore, the main aim of this review is to focus on important quinoxaline and quinoxaline-1,4-di-N-oxide analogues that have shown anti-TB activities, and their structure?activity relationships for designing anti-TB agents with better efficacies. The present review will be helpful in providing insights for rational designs of more active and less toxic quinoxaline-based anti-TB prodrugs.

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