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

  • Eur J Med Chem. 2014 Jul 23:82:466-71. doi: 10.1016/j.ejmech.2014.06.002.
Zhitao Zhang  1 ,  Jinlong Ma  1 ,  Li Zhu  1 ,  Yu Zhao  2
Affiliations
  • 1. Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
  • 2. Institute of Nautical Medicine, Nantong University, Nantong 226001, China. Electronic address: [email protected].
PMID: 24929344 DOI: 10.1016/j.ejmech.2014.06.002
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.

Keywords
Cleistanthin-A; Cleistanthoside-A; Inhibitor; Synthesis; Vacuolar H(+)-ATPase.