Design, synthesis and SAR bioevaluation of benzophenone-mercaptooxadiazole analogs

Abstract

Two novel series of the benzophenone tagged oxadiazoles were synthesized by cyclization of benzophenone hydrazide, followed by the nucleophillic alkylation of heterocyclic scaffold. Synthesized title compounds were characterized by the FT-IR, LCMS and NMR spectral techniques and were screened for the antibacterial, antifingal and anti-tuberculosis (anti-TB) activities. Biological screening of the synthesized target compounds reveals that, compound 7h was the potent cytotoxicant with lengthened activity against tubercular, bacterial and fungal agents. Compound 7h has morpholine group (six membered ring) attached to oxadiazole through two CH2 groups, methyl substituent at ortho-position and chlorine group at ortho-position of benzoyl ring. Compound 7h interacted through Vander Waal's interactions into the hydrophobic binding pocket, surrounded by the portions of Phe 41, Ile 122, Val 65, Phe 97, Ile 95, Gly 14, Asp 64, Ile 21, Phe 149, Asp 148, Met 147, Ser 94 and Ala 22. MIC value of the compounds for in-vitro anti-TB activity was 1.6 μg/ml. Keywords: Benzophenone, Oxadiazole, In-vitro and in-silico anti-TB, Morpholine, Piperidine