Design, synthesis, and biological evaluation of novel 4H-chromen-4-one derivatives as antituberculosis agents against multidrug-resistant tuberculosis

Authors: Zhao W, Wang B, Liu Y, Fu L, Sheng L, Zhao H, Lu Y, Zhang D
Publication: Eur J Med Chem
Keywords: 4H-chromen-4-one, Antitubercular agent, Multidrug-resistant tuberculosis, Polyketide synthase 13, Scaffold morphing
Software: ADMET Predictor®

Abstract

A series of 4H-chromen-4-one derivatives obtained by scaffold morphing of the benzofuran compound, TAM16, were tested for antitubercular activity. Compound 8d was active against drug-sensitive and multidrug-resistant tuberculosis. A preliminary druggability evaluation showed that compound 8d displayed favorable mouse and human microsomal stability, low cytotoxicity, and acceptable oral bioavailability. An in vivo study indicated that compound 8d exhibited modest efficacy in an acute mouse model of TB after 3 weeks of treatment. Thus, 8d is a promising antituberculosis lead compound.