Antitubercular Activity of Pyrrole Schiff bases and Computational Study of M. Tuberculosis InhA

Pursuing our search program for new antitubercular drugs we decided to explore the potentiality of pyrrole moiety by molecular modeling and synthesizing novel pyrrole Schiff bases analogues of phthivazid. Enoyl-acyl carrier protein reductase catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antitubercular drug target in Mycobacterium tuberculosis. The development of new antitubercular therapies is important both to combat potential drug-resistant bio weapons and to address the broader societal problem of increasing antitubercular resistance among many pathogenic bacteria. The in vitro activity of synthesized compounds were screened against Mycobacterium tuberculosis H37Rv, and some of these compounds have exhibited promising activity. Surflex molecular docking with InhA has shown putative binding modes of the designed compounds while the theoretical evaluation of cell permeability based on Lipinski’s rule of five has helped to rationalize the biological results.