Design, synthesis, biological activities and 3D-QSAR studies of quinazolinone derivatives containing hydrazone structural units

Abstract

In this study, three series of quinazolinone derivatives containing hydrazone structures were designed and synthesized. Bioactivity assays indicated that these compounds showed good antitumour activities towards human lung cancer cells (A549) and human prostate cancer cells (PC-3) and no apparent toxicity towards those nontumorigenic rat renal tubular epithelial cells (NRK-52E). In particular, compound 7n showed potent inhibitory activity towards A549 and PC-3 with IC₅₀ of 7.36 and 7.73 μmol L⁻¹, respectively. Subsequently, the relationships between the compound structures and numerous biological activities are discussed. A good predictive three-dimensional quantitative structure–activity relationship (3D-QSAR) model was constructed via CoMFA to direct the future structural units. The present results strongly show that 7n with the introduction of 2-fluorobenzoyl should be considered as a lead compound to develop novel antitumour agents.