Dhanji P. Rajani

Synthesis of benzimidazolyl-1,3,4-oxadiazol-2ylthio-N-phenyl (benzothiazolyl) acetamides as antibacterial, antifungal and antituberculosis agents

To affiliate multiple bioactivities in a compact heteronuclei, two series of benzimidazole based 1,3,4-oxadiazoles were synthesized and assessed in vitro for their efficacy as antimicrobial agents against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneri), four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) and Mycobacterium tuberculosis H37Rv and best results were observed amongst the N-benzothiazolyl aetamide series. The lipophilicity (LogP) influence on the biological profile (MICs) of the prepared products was also discussed. Upon biological screening, it was observed that the majority of the compounds were found to possess a significant broad spectrum antimicrobial (3.12-25 μg/mL of MIC) and antitubercular (6.25-25 μg/mL of MIC) potential. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

New 2-benzylsulfanyl-nicotinic acid based 1,3,4-oxadiazoles: Their synthesis and biological evaluation

A novel series of 5-(2-benzylsulfanyl-pyridin-3-yl)-2-(substituted)-sulfanyl-1,3,4-oxadiazoles 6a-j were synthesized from key intermediate 5-(2-benzylsulfanyl-pyridin-3-yl)-3H-[1,3,4]oxadiazole-2-thione 5. Nucleophilic substitution reactions with different electrophiles (E+), such as haloacetate and haloalkyl groups, were performed to get target compounds 6a-j. Compounds were characterized by NMR, mass, IR spectra and C, H, N analyses. All compounds were evaluated for their antimicrobial and antimycobacterial activities; selected analogs were screened for their anticancer activity on 60 tumor cell lines at single dose 1.00(-5) M. Unfortunately, none of the compounds showed a significant antitumor activity on 60 human tumor cell lines. However, compounds 6g and 6f with benzothiazole moiety (12.5 and 25 μg/ml) showed promising activity against Escherichia coli compared to ampicillin; compounds 6d, 6j bearing triazole and morpholine, respectively, showed promising antitubercular activity (25 μg/ml) compared to rifampicin.

A new class of 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazine analogues with antimicrobial/antimycobacterial activity.

This study presents the synthesis and in vitro pharmacological evaluations of novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in vitro antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneria) and four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) using paper disc diffusion and agar streak dilution method as well as against Mycobacterium tuberculosis H37Rv strain using BACTEC MGIT and Lowenstein-Jensen MIC method. The bioassay results indicate that nine compounds namely 5d, 5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u could be considered as possible potential agents with dual antimicrobial and antimycobacterial activities. The structures of the compounds were elucidated with the aid of IR, 1H NMR, 13C NMR, 19F NMR spectroscopy and CHN analysis.

A one pot, three component synthesis of coumarin hybrid thiosemicarbazone derivatives and their antimicrobial evolution

Abstract A convenient, one-pot, multi-component protocol for the preparation of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide derivatives has been achieved. Here, firstly we have reported the synthesis of 3-acetyl-2H-chromen-2-one using starch sulfuric acid and cellulose sulfuric acid as biodegradable catalysts. Subsequently, we also carried out the reaction of isothiocynates, hydrazine hydrate and 3-acetyl-2H-chromen-2-one in the presence of catalytic amount of glacial acetic acid in refluxing ethanol to afford corresponding 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide derivatives in high to excellent yields. All synthesized compounds were screened for antimicrobial activity. All compounds were found to show good to excellent activity against Escherichia coli MTCC 443.

In vitro and in vivo assessment of newer quinoxaline–oxadiazole hybrids as antimicrobial and antiprotozoal agents

A new series of N-(substituted-phenyl)-2-[5-(quinoxalin-2-yloxymethyl)-[1,3,4] oxadiazol-2-ylsulfanyl]-acetamides (5a-o) was designed and synthesised from the parent compound 2-hydroxy quinoxaline (1) through a multistep reaction sequence and was characterised by spectral and elemental analyses. All of the compounds synthesised were evaluated for their antimicrobial and antiprotozoal activities. The results revealed that quinoxaline-based 1,3,4-oxadiazoles displayed promising antibacterial, antifungal and anti-Trypanosoma cruzi activities compared with reference drugs, particularly the lead compound 5l in a short-term in vivo model in T. cruzi.

Synthesis, biological evaluation and docking study of some novel isoxazole clubbed 1,3,4-oxadiazoles derivatives

A novel series of isoxazole clubbed 1,3,4-oxadiazole derivatives have been synthesized by reaction of 5-(3-fluoro-4-methoxyphenyl) isoxazole-3-carbohydrazide with different substituted benzoic/pyridinyl/indolyl acids in phosphorous oxychloride, characterized by IR, 1H NMR, 13C NMR, MS analytical data and evaluated for their antimicrobial as well as antitubercular activity. Antibacterial activity of compounds 5e, 5g, 5h, 5j and 5l were found to be good against E. coli, P. aeruginosa, S. aureus and S. pyogenes as compared to standard Ampicillin. Compound 5b and 5i were found to be active antitubercular agents against M. tuberculosis H37Rv. Antibacterial and antitubercular activity was supported by molecular docking to gain insights of the mode of inhibition of MurD ligase enzyme.

Newer thiazolopyrimidine-based sulfonamides clubbed with benzothiazole moiety: synthesis and biological evaluation

A new class of thiazolopyrimidine-based sulfonamides (5a–j) was synthesized from a parent compound 2-methoxy benzoic acid by multistep reaction in order to find new agents to fight against microbial infections. Substituted thiazolopyrimidines (3a–e) were prepared by cyclocondensation of substituted thiazolidinediones (2a–e) with urea in the presence of acid catalyst P2O5. Finally, desired compounds (5a–j) were synthesized from intermediates (4a–e) prepared from compounds (3a–e) by chlorosulfonation followed by condensation with corresponding benzothiazole moiety. The synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR spectral data, and elemental analysis, and were evaluated for in vitro antimicrobial activity against certain bacterial and fungal strains using the broth microdilution method as well as antitubercular activity against H37Rv using Lowenstein–Jensen agar method.

Benzene sulfonamide pyrazole thio-oxadiazole hybrid as potential antimicrobial and antitubercular agents

To fulfil the development goals towards the synthesis of innovative, potent and highly effective antimicrobial and antimycobacterial agents, a set of benzene sulfonamide pyrazole thio-oxadiazole derivatives (6a–6l) have been synthesized by the reaction of 4-[5-(3-fluoro-4-methoxyphenyl)-3-(5-mercapto-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl]benzenesulfonamide with alkyl/aryl halides, identified by IR, NMR (1H, 13C, 19F) and MS data. Composed compounds were examined for their antimicrobial and antitubercular activity. Antibacterial activity of compounds 6c, 6d, 6j and 6l was found promising against E. coli, P. Aeruginosa, S. Aureus and S. Pyogenes as compared to standard ampicillin. Compounds 6d, 6e, 6g, 6h and 6i were found active against tubercular strain H37Rv. Molecular docking studies against mycobacterium tuberculosis β-ketoacyl-acyl carrier protein synthase A (Kas-A) was carried out which suggests a possible mode of inhibition for this target protein and the potential of synthesized compounds as antitubercular agents.