A A Molecular hybridization approach to design and study the in vitro and in silico properties of N-phenyl-4-oxo-butanamide derivatives

Abstract

In the present study, we have used molecular hybridization approach to design and synthesise N-phenyl-4-oxo-butanamide derivatives as potent anti-TB agents. A total of 28 target compounds were synthesized. Among the tested compounds, 4c: N-(2,4-difluorophenyl)-4-oxo-4-(4-phenylpiperazin-1-yl) butanamide and 4d: N-(2,4-difluorophenyl)-4-oxo-4-(4-benzylpiperazin-1-yl) butanamide, were identified as potent anti-TB agents with an MIC = 1.56 µg/ml against M. tuberculosis H37Rv. Interestingly these compounds didn’t show appreciable antibacterial and no antifungal activity, clearly indicating their selectivity towards M. tuberculosis. Docking simulation on enzymes involved in mycolic acid biosynthesis resulted in identification of InhA as the putative enzyme target for these compounds. In the study our compounds 4c and 4d showed highest binding affinity of below -10.0 KCal/mol.