Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H+-ATPase inhibitors

Abstract The concise syntheses of two natural diphyllin glycosides Cleistanthin-A ( CA ), Cleistanthoside-A ( CleA ) and its derivative, Cleistanthoside-A tetraacetate ( CleT ), have been achieved. They were evaluated for their in vitro anti-proliferative activities against MCF-7, HeLa, HepG2, HCT-116, U251 cancer cell lines by MTT assay. Both of CA and CleT were anti-proliferative to these cancer cells at nanomolar concentrations. They have been shown to inhibit the activity of vacuolar H + -ATPase (V-ATPase) in HepG2 cells and neutralize the pH of lysosomes at nanomolar concentrations.