Synthesis, biological evaluation and structure-activity relationship of 2-styrylquinazolones as anti-tubercular agents

2-Styrylquinazolones are reported as a novel class of potent anti-mycobacterial agents. Forty-six target compounds have been synthesized using one pot reaction involving isatoic anhydride, amine, and triethyl orthoacetate followed by aldehyde to construct the 2-styrylquinazolone scaffold. The anti-mycobacterial potency of the compounds was determined against H(37)Rv strain. Twenty-six compounds exhibited anti-Mtb activity in the range of 0.40-6.25 mu g/mL. Three compounds 8c, 8d and 8ab showed MIC of 0.78 mu g/mL and were found to be non-toxic (<50% inhibition at 50 mu g/mL) to HEK 293T cell lines with the therapeutic index >64. The most potent compound 8ar showed MIC of 0.40 mu g/mL with the therapeutic index >125. An early structure activity relationship for this class of compounds has been established. The computational studies indicate the possibility of these compounds binding to the penicillin binding proteins (PBPs). (C) 2016 Elsevier Ltd. All rights reserved.