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Synthesis and biological evaluation of some new benzofuran derivatives

5-Chloro-3-methyl-2-benzofuran carbohydrazide (4) upon treatment with potassium isothiocynate in presence of hydrochloric acid in water gave 5-chloro-3-methylbenzofuran-2-carbo-N-thiosemicarbazide (5). The cyclisation of 5-chloro-3-methylbenzofuran-2-carbo-N-thiosemicarbazide (5) under different reaction conditions offered 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,2,4-triazole, thiazolidinone and thiopyrimidinone. The structures of these compounds were established on the basis of spectral data. Some of these compounds exhibited good antimicrobial activity.

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Design and synthesis of novel 1-((dimethylamino)methyl)-3-(4-(3-(substitute dphenyl)-4-oxothiazolidin-2-yl)phenylimino)-5-nitroindolin-2-ones as potent antitubercular agents

Objective: Isatins have emerged as antimicrobial agents due to their broad spectrum of in vitro and in vivo antimicrobial activities. In addition, thiazolidinone also reported to possess various biological activities particularly antimicrobial activity. Due to the importance, we planned to synthesize compounds with isatin functionality coupled with thiazolidinone as possible antitubercular and antimicrobial agents which could furnish better therapeutic results. Methods: In vitro Mycobacterium tuberculosis method and agar streak dilution test are used to estimate antitubercular and antimicrobial potency of title analogs, respectively. Minimum inhibitory concentration of entire title compounds was determined against all tested microorganism such as M. tuberculosis, four Gram-positive, three Gram-negative bacteria, and two fungi. Results: A series of new thiazolidinone substituted Schiff and Mannich bases of 5-nitroisatins were designed and synthesized by a multistep synthesis from isatin. Structures of synthesized compounds are characterized using Fourier-transform infrared, proton nuclear magnetic resonance, mass spectroscopy, and bases of elemental analysis. Mild to good antitubercular and antimicrobial activity was showed by synthesized 5-nitroisatin analogs. The relationship between the biological activity and the functional group variation of the tested compounds was discussed. Conclusion: 3-(4-(3-(4-Aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethyl amino)methyl)-5-nitroindolin-2-one 6 and 3-(4-(3-(2-aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethylamino)methyl)-5-nitroindolin-2-one 13 were found to be the most potent compounds of this series which might be extended as a novel class of antimicrobial agents.

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Studies on aromatic schiff bases from methyl-1-naphthyl ketone. Part-I: Synthesis and characterization of ketimines from 1-acetylnaphthalene with derivatives of aniline

Schiff bases(Ketimines) were prepared from Methyl-1-naphthyl-ketone with 2-Hydroxy-aniline, 3-Hydroxyaniline, 4-Hydroxy-aniline, 3-Nitroanilines and 4-Bromo-aniline using toluene as solvent by azeotropic(reflux) method using Dean and Stark. The synthesized ketimines were characterized by colour, physical constants, TLC and FTIR spectra. The purity of the synthesized compounds was confirmed from the information gathered from TLC, elemental and FTIR spectral analysis.

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Nutrition and immunity in elderly

Aging is associated with increase in chronic disease as well as infections and associated morbidity. This is often throughout to be secondary immunosenescene. Whether this decline in immune function with aging is due to the aging process per Se or is secondary to poor health, inflammation, and other life style factors particularly suboptimal nutritional status. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and in creased susceptibility to infections. Antioxidant vitamins and trace elements [vitamins C, E, selenium, copper and zinc] counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redoxsensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B[6], folate, B[12], C,E, and of selenium, Zn, copper and iron supports a Th I cytokine-mediated immune response with sufficient production of proinflammatory cytokine. Vitamin A and D play important roles in both cell mediated and humoral antibody response. Nutrient supplementation is often accompanied by an improvement in immune function.

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Tricyclic sulfones as orally active gamma-secretase inhibitors: Synthesis and structure-activity relationship studies

Tricyclic sulfones were designed as gamma-secretase inhibitors and found to have excellent potency. Extensive SAR shows that a large number of sulfonamides at position 7 of the tricycle are very well tolerated. Compounds such as 15a and 15c showed remarkable in vivo potency.

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Use of human tissue in ADME and safety profiling of development candidates

The clinical success of a compound is often curtailed because of inadequate safety, pharmacokinetics or efficacy. Human tissue can be used to identify the potential shortcomings of new drugs before they undergo testing in man. This review highlights the consent and ethical approval required for the use of human tissues and discusses their use for predicting human ADME and safety profiles of drugs in preclinical development. The ability to retrieve a wide range of viable tissues from human donors provides the opportunity to test drugs for many potential use-limiting side-effects.

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Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection

Over 170 million people are chronically infected by the hepatitis C virus (HCV) andat risk fordyingfromliver cirrhosis and hepatocellular carcinoma. Current therapy is expensive, associated with significant side effects, and often ineffective. Discovery of antiviral compounds against HCV traditionally involves a priori target identification followed by biochemical screening and confirmation in cell-based replicon assays. Typically, this results in the discovery of compounds that address a few predetermined targets and are prone to select for escape variants. To attempt to identify antiviral compounds with broad target specificity, we developed an unbiased cell-based screening system involving multiple rounds of infection in a 96-well format. Analysis of a publicly available library of 446 clinically approved drugs identified 33 compounds that targeted both known and previously unexplored aspects of HCV infection, including entry, replication, and assembly.Discovery ofnovel viral and cellular targets in this manner will broaden the therapeutic armamentarium against this virus, allowing for the development of drug mixtures that should reduce the likelihood of mutational escape.

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Computational screening of drugbank database for novel cell cycle inhibitors

The cell cycle is governed by a family of proteins i.e. cyclin dependent kinases (CDKs) and their inhibitors (CDKIs) through activating and inactivating events. Cdks are heteromeric serine/threonine kinases that control progression through the cell cycle in concert with their regulatory subunits, the cyclins. CDK activity was found to increase in different types of human tumors as well as progression and/or invasiveness of some cancers such as breast, leukemia, and melanoma. Computer aided drug design was implemented to find novel compounds as possible CDK inhibitors. Screening of 1400 drugs from DrugBank database was carried out using Molegro software against various CDKs derived from Protein Data Bank. From the result, the best three drugs which exhibited high binding affinity against all targets are reported. The analysis against eight proteins resulted in 14 drugs and the top three drugs obtained are Olmesartan, Verteporfin and Atorvastatin.

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QSAR Studies of thiazolidinone derivatives as antimicrobial agents

QSAR (Quantitative Structure-Activity Relationship) relate biological activity data along with the physiochemical and structural properties of a group of compounds. In general, most of the medicinal compounds involve heterocyclic compounds containing nitrogen and sulphur especially thiazolidinones they possess a broad spectrum antimicrobial activity. In the present study, we have carried out the QSAR studies of antimicrobial thiazolidinones using Hansch analysis. The results of QSAR studies indicated that the antimicrobial activity of thiazolidinones are mainly governed by the topological parameters, kiers 3rd order alpha shape index (kappa alpha 3) and second order valence connectivity index (2chinu) along with the lipophilic parameter, log of octanol water partition coefficient (log P).

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Synthesis, characterization and antimicrobial evaluation of novel quinoline based 2-azetidinones and 4-thiazolidinones

The present work describes the synthesis of a series of quinoline based 4-thiazolidinone and 2-azetidinone derivatives from Schiff bases obtained from the condensation of 2-chloro-3-formylquinoline and 3-4-aminoacetophenones. Quinoline based 4-thiazolidinone and 2-azetidinone derivatives have been prepared by the reaction of various substituted Schiff base with thioglycholic acid and chloroacetyl chloride, respectively. The intermediate Schiff bases were synthesized by the condensation of different quinoline aldehydes with amino acetophenones. The starting compound i.e aldehyde was synthesized through Vilsmeier reaction from respective acetanilides. The synthesized compounds were characterized by their physical and spectral data. The synthesized compounds were screened for their antibacterial and antifungal activities by using cup plate method against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, 25, 50, 100 mug/mL concentration using ciprofloxacin as reference standard drug and Aspergillus Niger, Candida albicans as same concentration using clotrimazole as reference drug, respectively. The spectral data of synthesized compounds of (3a-f), (4a-e) and (5a-f) were characterized by ES Mass, 1H-NMR, IR spectrophotometric methods. The antimicrobial results revealed that the quinoline based Schiff bases, azitidinone and thiazolodinones analogues showed good activity towards Gram (+) bacteria as compared to ciprofloxacin. These compounds showed decent activity against Gram (-) bacteria.

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