Nano-CuFe 2 O 3 -catalyzed green synthesis of novel quinazolinone-tetrazole hybrids as anti-cancer agents

A novel green protocol has been developed for the synthesis of quinazolinone-tetrazole conjugates (7a-g, 8a-g and 9a-g) using recyclable nano-CuFe O catalyst in water. Initially, 2-mercapto-3-substituted phenethylquinazolin-4(3H)-one (5a-c) was prepared by using nano-CuFe O catalyst in water. Then, compounds (5a-c) were reacted with 1-bromo-3-chloropropane under nano-CuFe O catalyst in water solvent to give S-alkylated quinazolinone core intermediate (6a-c), which was subsequently reacted with 1-substituted-1H-tetrazole-5-thiol (2a-g) by employing the similar reaction conditions to afford the final target compounds. The regioselective formation of C-S bond was unambiguously confirmed by single-crystal X-ray diffraction. The anti-cancer activity of the derivatives on various cancer cell lines such as SIHA, MD-AMB-231 and HepG2 was evaluated. Remarkably, compounds, 7f, 8f, 9a, 9d and 9f, showed potent activity in MD-AMB-231 cancer cell line (IC : 9.13-10.3 µM), while the same derivatives showed significant potent activity in SiHa and HepG2 cancer cell lines (IC : 17.46-27.0 µM). Most significantly, compound 7o (IC : 8.15 µM) showed potent activity, compared to the drug etoposide (IC : 18.11 µM) against MD-AMB-231 cell line. Flow cytometry analysis revealed that compounds 7f, 8f, 9a, 9d and 9f arrested the cell growth in the G1 phase in MD-AMB-231 cell line.