Chemical synthesis and in silico molecular modeling of novel pyrrolyl benzohydrazide derivatives: Their biological evaluation against enoyl ACP reductase (InhA) and Mycobacterium tuberculosis

Abstract

In efforts to develop new antitubercular agents, we report here the synthesis of a series of novel pyrrole hydrazine derivatives. The molecules were evaluated against inhibitors of InhA, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of the mycobacterial cell wall as well as inhibitors of Mycobacterium tuberculosis H37Rv. The binding mode of compounds at the active site of enoyl-ACP reductase was explored using the surflex-docking method. The model suggests one or two H-bonding interactions between the compounds and the InhA enzyme. Some compounds exhibited good activities against InhA in addition to promising activities against M. tuberculosis.

Keywords: Antitubercular activity; Enoyl-ACP reductase; Molecular modeling; Pyrroles.