Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases.

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds , , and possessed potent cytotoxic activity against PC-3 cells with IC 3.56, 8.99, and 10.22 µM, respectively. Compound displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC 8.5 µM. Moreover, compound exhibited potent inhibitory activity on EFGR with IC 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways.