Synthesis and evaluation of coumarin derivatives as potential anticancer therapies for colon cancer: In vitro antiproliferation, cell cycle arrest analyses, network pharmacology investigations, and molecular docking studies.

In this study, a series of coumarin derivatives (1-25) were synthesized and characterized. The antiproliferative activities of these derivatives were systematically evaluated against two human cancer cell lines, HCT116 and SKOV3, using the CCK-8 viability assay. The results showed that derivatives 24 and 25 exhibited significant inhibitory activities against HCT116 cells (IC50 = 8.48 ± 0.92 μM) and (IC50 = 8.95 ± 0.67 μM), respectively, while derivative 25 also demonstrated good inhibitory activity against SKOV3 cells (IC50 = 22.27 ± 2.66 μM). Notably, when derivatives 24 and 25 were combined with paclitaxel, they significantly enhanced the S-phase cell cycle arrest. Subsequently, network pharmacology analysis of derivative 24 revealed that CTNNB1 was the most deeply colored target and exhibited the highest number of connections with other targets. Docking analysis indicated that derivative 24 could activate CTNNB1 by interacting with the GLN-302 and ARG-342 residues of the protein. Derivatives 24 and 25 are promising anticancer drug candidates derived from natural products.