title: Synthesis and Evaluation of Cleistanthin A Derivatives as Potent Vacuolar H(+) -ATPase Inhibitors.
abstract: Twelve new glycosides and alkane derivatives of cleistanthin A were designed and synthesized. Their in vitro antiproliferative activity was investigated against HCT-116, HepG2, A549, Hela tumor cell lines and HEK293 cell by MTT assay. Most of these compounds displayed antiproliferative effects on four cancer cells at submicromolar concentration, but they were less potent than cleistanthin A Moreover, they showed no antiproliferative effects on HEK293 cell at 200 nm. The most potent compounds, 3e and 4a, have been shown to inhibit the activity of vacuolar H(+) -ATPase (V-ATPase) and neutralize the pH of lysosomes at submicromolar concentrations.
authors: Institute of Nautical Medicine, Nantong University, Nantong, 226001, China.
authors: Yu
authors: Y
authors: Zhao
authors: Institute of Nautical Medicine, Nantong University, Nantong, 226001, China.
authors: Yapeng
authors: Y
authors: Lu
authors: Institute of Nautical Medicine, Nantong University, Nantong, 226001, China.
authors: Jinlong
authors: J
authors: Ma
authors: Institute of Nautical Medicine, Nantong University, Nantong, 226001, China.
authors: Li
authors: L
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry*; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017705:Lignans / Q000737:chemistry*; D008247:Lysosomes / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006027:Glycosides; D017705:Lignans; C010088:cleistanthin; D025262:Vacuolar Proton-Translocating ATPases
keywords: Cleistanthin A; inhibitor; synthesis; vacuolar H+-ATPase