Potential anti-proliferative agents from 1,4-benzoxazinone-quinazolin-4(3H)-one templates

Abstract

A novel synthetic protocol has been developed for the synthesis of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids 7a-n by employing Pd-catalyzed CH arylation in presence of 5-10% phosphine ligand in good to excellent yields and evaluated for their anti-proliferative activity against three cancer cell lines such as A549 (lung), HeLa (cervical), MDA-MB-231 (breast). Compounds 7d, 7f, 7l and 7n exhibited promising anti-proliferative activity with GI₅₀ values ranging from 0.37 to 2.73 µM respectively against A549, HeLa, and MDA-MB-231, while compound 7f showed significant activity against MDA-MB-231 with GI₅₀ value 0.58 µM, 7j showed significant activity against A549 with GI₅₀ value 0.32 µM and 7l showed significant activity against HeLa with GI₅₀ value 0.37 µM. This is the first report on the synthesis and in vitro anti-proliferative evaluation of 1,4-benzoxazinone-acetylphenylallyl quinazolin-4(3H)-one hybrids.

Keywords: 1,4-Benzoxazinone; Apoptosis; CC Coupling; Cell lines; Quinazolinone anti-proliferative.