Synthesis and In vitro Cytotoxic Evaluation of New Quinazolinone-Based Chalcones

Abstract

Chalcones are a class of compounds with a wide range of biological activities. In addition, derivatives based on the quinazolinone skeleton are currently of interest to research in the screening of compounds with cytotoxic effects. Compounds containing chalcone structures on the basis of quinazolinone can yield new structures with cytotoxic effects. This article presents the synthesis of new quinazolinone-based chalcones 8a-j via a three step-procedure. The first step is the condensation of 5-hydroxyanthranilic acid (5) with acetic anhydride at reflux for 2 h to afford intermediate 6 in 87%. This intermediate was then reacted with 4-aminoacetophenone in acetic acid at reflux for 14 h to give 7 in 77 %. Finally, the reaction of 7 with different aldehydes in ethanol in the presence of NaOH at room temperature for 14 h furnished target compounds 8a-j in 57 - 75%. The structure of synthesized compounds was confirmed using 1H, 13C NMR and MS spectra. The bioassay results showed that several compounds displayed cytotoxic activity against two cell lines including HepG-2 and SKLu-1. Among synthesized compounds, 8c exhibited the strongest cytotoxic activity against SKLu-1 with IC50 value of 20.10 µM.