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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords

• 1,3,4-Oxadiazole
• Docking
• Simulation
• M. tuberculosis
• ADMET studies