Antitumor and multikinase inhibition activities of some synthesized coumarin and benzofuran derivatives

Two new series of coumarin and benzofuran derivatives were designed, synthesized, and assessed for their in vitro and in vivo antitumor activities against breast cancer. Compounds 8, 9, 14, 15, and 17 exhibited the best antiproliferative activities (IC50: 0.07-2.94 mu M) against the MCF-7 cell line, compared with lapatinib (IC50: 4.69 mu M). Compound 14, with the most potent cytotoxic activity against MCF-7 cells, was capable of enhancing preG1 apoptosis and triggering cell cycle arrest at the G2/M phase. The kinase inhibitory activity of compound 14 against a panel of 22 kinases was examined to reveal multikinase inhibition within -39% to -97%. Furthermore, compound 14 exhibited potent in vivo Ehrlich (mammary adenocarcinoma) tumor regression, positive caspase-3, and negative EGFR immunoreaction, and was capable of elevating the catalase level. The physicochemical properties and pharmacokinetic parameters of compound 14 were investigated in silico for its druglikeness.

Automated summary

Two series of coumarin and benzofuran derivatives were synthesized and evaluated for their antitumor activities against breast cancer. Compound 14 exhibited the best antiproliferative and cytotoxic activities, as well as kinase inhibitory activity. It also showed potent in vivo tumor regression and elevated catalase level.