Design, synthesis, biological evaluation and molecular modeling of new coumarin derivatives as potent anticancer agents.

A novel series of coumarin-pyridine/fused pyridine hybrids were designed and synthesized. Their anticancer activity was evaluated against human cancer cell lines MCF-7, HCT-116, HepG-2, and A549. Compounds 9, 10, and 11 showed the most potent growth inhibitory activities with IC₅₀ values ranging from 1.1 to 2.4 μM, against MCF-7 cell line. Flow cytometric analysis revealed that these compounds induced cell cycle arrest in the G2/M phase followed by apoptotic cell death. Consistent with these results, the activity of caspase-3 in MCF-7 cells was tested. The results indicated that compounds 9, 10, and 11 increased caspase-3 activity significantly compared to control group. Moreover, their binding affinity for caspase-3 was confirmed by docking study. Taking all these data together, it is suggested that these coumarin derivatives may be potential antiproliferative agents. [ABSTRACT FROM AUTHOR]