Studies on the Design Synthesis and Evaluation of Some Novel Heterocyclic Compounds for Antimicrobial and Antitubercular activities

Abstract

In an approach to combat the growing antimicrobial resistance and to develop more potent and less side effects antibacterial, antifungal and anti-tubercular agents, we have synthesized some novel 2,5-disubstituted-1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole compounds. Substituted anilines were condensed with chloroacetic acid in the presence of ethanol to give 2-(susbtituted phenylamino)acetic acids(1a-f), these acids on treating with dry ethanol in presence of concentrated sulphuric acid to form esters(2a-f) and these esters on treating with hydrazine hydrate(99%) resulted to 2-(substituted phenylamino)acetohydrazide (3a-f), when these hydrazide condensed with carbondisulphide under strong basic conditions with potassium hydroxide to give 5-((2,4-disubstituted phenylamino)methyl)-1,3,4-oxadiazole-2-thiol(4a-f). The hydrazide condensed with carbondisulphide and sulphuric acid in the presence of ethanol give 5-((2,4-disubstituted phenylamino)methyl)-1,3,4-thiadiazole-2-thiol(5a-f). Further 5-((2,4,5-trisubstitutedphenylamino)methyl)-4-phenyl-4H-1,2,4-triazole-3-thiol(6a-f) was obtained on treatment with aryl isothiocyanate with 4N-NaOH in ethanol. These oxadiazole/thiadiazoles/triazole when treated with phenacyl bromide or p-substituted phenycyl bromide, in presence of dimethyl sulfoxide afford a new series of 1-(4-substitutedphenyl)-2-(5-((substitutedphenylamino)methyl)-1,3,4-oxadiazol/thidiazol/triazol-2-ylthio)ethanone (7a-r), (8 a-r) and (10a-r). All these newly synthesized compounds (7a-r), (8a-r) and (10a-r) were screened for antibacterial, antifungal and anti-tubercular study. In-vitro anti-bacterial activity results indicated that 7e, 7f, 7k, 7r, 8d, 8f, 8k, 8r, 10e, 10f, 10l and 10r have shown good activity against E.coli, P.aeruginosa and S.aureus with MIC values between 8 to 16µg/ml. All compounds were tested fungal strains at 1-64 µg/ml concentration. Some of the compounds 7e, 7f, 7p, 7r, 8e, 8f, 8p, 8r, 10e, 10k, 10l and 10r showed good activity against C.Albicans, C. neoformans and A.Niger with MIC values between 4 to 16µg/ml. And all the compounds were screened for anti-tubercular activity by using MABA method. Compounds 7e, 7f, 7k, 7p, 7r, 8f, 8k, 8p, 8r, 10d, 10e, 10p and 10r showed good anti-tubercular activity with MIC values between 8 to 16µg/ml. The presence of electron withdrawing groups like Cl and F on the phenyl ring of 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole nucleus are crucial for anti-microbial and anti-tubercular activity. newline