Two novel series of quinazolinone-based hybrids, including quinazolinone-1,3,4-oxadiazoles (10a–l) and
quinazolinone-1,3,4-oxadiazole-benzimidazoles (8a–e), were designed and synthesized and their cytotoxic
activities against three human cancer cell lines, lung cancer (A549), cervical cancer (HeLa), and breast cancer
(MCF-7), were evaluated. The cytotoxic assays revealed that 10i with a lipophilic 4-fluoro-phenyl moiety
at the C-2 position of the quinazolinone ring displayed good cytotoxicities against the A549 and MCF-7
cell lines, while 8b–d with the thioether-linked benzimidazole moiety incorporated on the right side of the
oxadiazole ring induced comparable stronger activities toward the MCF-7 cell line, relative to the simple
two-heterocycle-containing hybrid 10i. These novel quinazolinone-based hybrids could be considered as lead
compounds that merit further optimization and development as anti-cancer agents.