Synthesis and anti-tubercular evaluation of some novel (E)-5-(4-(benzylidene amino) phenyl)-1,3,4-oxadiazole-2-thiol derivatives

Tuberculosis remains a ninth global health cause affecting millions of people. The susceptibility and resistance caused by first and second-line drugs have not changed for decades. There is a need to develop novel drugs with better pharmacological profiles. In this study, a series of (E)-5-(4-(benzylidene amino) phenyl)-1,3,4-oxadiazole-2-thiol derivatives were synthesized, docked, and ADMET studies were performed. Based on binding affinity, the compounds were evaluated for their ability to inhibit the M. tuberculosis H37Rv strain. The compounds showed binding energy between −8.2 and −10.0 Kcal/mol. Molecular simulations benefited the representation of the actual biological conditions with a significant outcome. The compound 5-(4-{(E)-[(2-nitrophenyl) methylidene] amino} phenyl)-1,3,4-oxadiazole-2-thiol (R4) showed the best binding −10.0 Kcal/mol, MIC of 0.8 µg/ml, the IC50 value of 49.01 and the Selectivity Index of 61.33. The synthesized compounds were evaluated for anti-mycobacterial activity against M. tuberculosis (H37Rv) using MABA assay and compared with the standards; R3 and R4 were sensitive at 0.8 µg/ml. Among the designed compounds 5-(4-{(E)-[(2-nitrophenyl)methylidene]amino}phenyl)-1,3,4-oxadiazole-2-thiol showed the best activity with higher IC50 values. As a result, molecular hit can be good lead for further development for tuberculosis treatment.