Synthesis of xanthone derivatives and anti-hepatocellular carcinoma potency evaluation: induced apoptosis

Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique. Their in vitro inhibition potency against the growth of four cancer cell lines was evaluated. XD-1 ∼ [6,9,10-trihydroxy-3,3-dimethyl-5-(2-methylbut-3-en-2-yl)-3 H ,7 H -pyrano[2,3- c ]xanthen-7-one] was confirmed as the most active agent against HepG2 cell line growth with IC 50 of 18.6 ± 2.31 μM. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for XD-1. XD-1 arrested HepG2 cells on the G0/G1 phase, as indicated by the decreased expressions of cyclin D and CDK2 and the increased expressions of p21. Western blot implied that XD-1 regulated p53/MDM2 to a better healthier state. Moreover, XD-1-induced cell apoptosis was mitochondrion-mediated, as evidenced by caspase activation and involved the PI3K/AKT/mTOR signaling pathway. All the evidence supports that XD-1 is a significant anti-cancer agent for HCC. Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique.