Synthesis and biological evaluation of new 1,3,4-thiadiazole derivatives as potent antimicrobial agents

Abstract

A series of 1,3,4-thiadiazole derivatives were designed and synthesized using N-(4-nitrophenyl)acetohydrazonoyl bromide and 1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethan-1-one as starting materials. The treatment of 1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethan-1-one with methyl hydrazinecarbodithioate or hydrazinecarbothioamide afforded 2-[1-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethylidene]hydrazine derivatives. The targeted 1,3,4-thiadiazolyl derivatives were prepared by the reaction of 2-[1-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethylidene]hydrazine derivatives with hydrazonoyl chloride derivatives. The reaction of N-(4-nitrophenyl)acetohydrazonoyl bromide with 2-[(methylthio)carbonthioyl]hydrazones in absolute ethanol in the presence of triethylamine afforded the corresponding 1,3,4-thiadiazole derivatives. The newly synthesized compounds were fully characterized by 1H NMR, 13C NMR, IR, MS, and elemental analysis. Moreover, the antimicrobial activity of the synthesized 1,3,4-thiadiazole derivatives were tested against E. coli, B. mycoides, and C. albicans. Four compounds outperformed the other produced compounds in terms of antimicrobial activity.Graphical abstract