Design, Synthesis, Anti-tubercular and Docking Studies of Novel 2-Furanyl-3-substituted Quinazolin-4-one Derivatives

Abstract

In this work, the synthesis, characterization and the anti-tubercular activity of novel 2-furanyl-3- substituted quinazolin-4-one derivatives and also predicted their affinity against Mycobacterium tuberculosis enoyl acyl carrier protein reductase were carried out. The targeted compounds were synthesized by the condensation of 2-(furan-2-yl)-4(3H)-1-benzoxazine-4-one with different primary amines. After structural elucidation using spectral data, the compounds were screened for anti-tubercular activity against Mycobacterium tuberculosis H37RV strain. The binding affinity against enoyl acyl carrier protein reductase was predicted using MOE and FITTED docking tools. The synthesized compounds showed a promising anti-tubercular activity in the range from 12.5 to 100 μg/mL. According to MOE docking, the common amino acids in the active site of InhA were found to form hydrogen bonding and hydrophobic interactions with the synthesized quinazolinones. Docking simulations also showed that an aromatic side chain capable of forming hydrogen bond interactions can increase affinity of 2-furanyl quinazolinones to enoyl acyl carrier protein reductase.