Synthesis of 4-Phenyl-4,5-dihydropyranopyrazolone Derivatives with Activated Potassium Carbonate: Evaluation of Anticancer Activity on Cancer Cell Lines and Apoptosis Mechanism

A green and efficient one-pot, four-component synthesis of 4-phenyl-4,5-dihydropyranopyrazolone derivatives 5a–5l is described in ethanol-water with activated potassium carbonate and evaluation of anticancer activity on cancer cell lines and apoptosis mechanism is also investigated. This method provides several advantages such as environmental friendliness, shorter reaction time, excellent yields, and simple workup procedure. The in vitro cytotoxic activity of the synthesized compounds was investigated against cancer cell lines (PC-3, MCF-7, and A-2780) in comparison with doxorubicin, a well-known anticancer drug, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide colorimetric assay. Also apoptosis studies were investigated by caspase-3 and caspase-9 enzymes and mitochondrial membrane potential. Our compounds showed acceptable and moderate cytotoxicity compared with doxorubicin in the studied cell lines. The compounds 5g in PC3 cell line (half maximal inhibitory concentration (IC50= 104 μM)), 5g and 5i in MCF7 cell line (IC50 = 23 and 87 μM, respectively), and 5g–5i in A2780 cell line (IC50 = 60, 50, and 31 μM, respectively) showed the best results close to the control drug doxorubicin. The compound 5h showed significant result in the activation of caspase-3 and caspase-9 enzymes in comparison with the control. Only the 5g in MCF7 cells and the 5g–5i derivatives in A2780 cells caused increased mitochondrial membrane potential compared to the control group.