New oxadiazole derivatives of isonicotinohydrazide in the search for antimicrobial agents: Synthesis and in vitro evaluation

Abstract

Structural modifications of the front line antitubercular drug isoniazid provide lipophilic adaptations of the drug in which the hydrazide moiety of isoniazid is replaced by 1,3,4-oxadiazole heterocycles to eliminate in vivo acetylation by arylamine N-acetyltransferase, which results in the formation of inactive acetylated drug. In the present study, a series of sixteen oxadiazole derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR and mass spectral studies. All the synthesized compounds were evaluated for their antimicrobial activity by broth dilution method against two Gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus), two Gram-negative bacterial strains (Pseudomonas aeruginosa and Escherichia coli) and two fungal strains (Candida albicans and Aspergillus niger). The minimum inhibitory concentrations of the compounds were in the range of 1.56-50 g ml-1 against the bacterial and fungal strains. The results revealed that all the synthesized compounds have a significant biological activity against the tested microorganisms. Among the synthesized derivatives 4g, 4h, 4m and 4p were found to be the most effective antimicrobial compounds. Copyright 2012 (CC) SCS.