title: 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.
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China. Electronic address: zhaoyoo@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects; D061986:MCF-7 Cells; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D004187:Disaccharides; D004791:Enzyme Inhibitors; D006027:Glycosides; D017705:Lignans; C579714:cleistanthoside A tetraacetate; C010088:cleistanthin; D025262:Vacuolar Proton-Translocating ATPases
keywords: Cleistanthin-A; Cleistanthoside-A; Inhibitor; Synthesis; Vacuolar H(+)-ATPase