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

Abstract

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 H₃₇Rv strain. Twenty-six compounds exhibited anti-Mtb activity in the range of 0.40–6.25 μg/mL. Three compounds 8c, 8d and 8ab showed MIC of 0.78 μg/mL and were found to be non-toxic (<50% inhibition at 50 μg/mL) to HEK 293T cell lines with the therapeutic index>64. The most potent compound 8ar showed MIC of 0.40 μg/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).