Camptothecin derivatives induce apoptosis and inhibit proliferation of prostate cancer PC-3M cells through downregulation of PI3K/Akt signaling pathway

Malignant tumors are increasing the human mortality rate year by year, so there is an urgent need to develop novel and highly effective drugs. Camptothecin (CPT) is a natural medicinal product with broad-spectrum antitumor activity. In this study, 11 CPT derivatives were synthesized. Their antitumor activities were evaluated by CCK-8, morphological observation, plate cloning, scratching, DAPI staining, cell cycle, and apoptosis. The conformational relationships were also analyzed by molecular docking and 3D-QSAR. The results showed that the CPT derivatives showed significant inhibitory effects on all five tumor cell lines, A549, HepG2, MCF-7, HemECs, and PC-3M, with the best inhibitory ability against PC-3M in prostate cancer. Among all derivatives, compound 5 had the lowest IC50 value of 0.0881 μM. In addition, compound 5 regulated the downstream cascade response by inhibiting the PI3K-Akt signaling pathway, causing cycle arrest and apoptosis. The predicted results of molecular docking and 3D-QSAR were consistent with those of the experimental group. This demonstrates the anti-tumor potential of compound 5.