Synthesis and Evaluation of Cleistanthin A Derivatives as Potent Vacuolar H(+) -ATPase Inhibitors.
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.
['Zhao|Yu|Y|', 'Lu|Yapeng|Y|', 'Ma|Jinlong|J|', 'Zhu|Li|L|']
D000970:Antineoplastic Agents D045744:Cell Line, Tumor D049109:Cell Proliferation D060326:Chemistry Techniques, Synthetic D015195:Drug Design D004354:Drug Screening Assays, Antitumor D004791:Enzyme Inhibitors D006027:Glycosides D057809:HEK293 Cells D006801:Humans D006863:Hydrogen-Ion Concentration D017705:Lignans D008247:Lysosomes D025262:Vacuolar Proton-Translocating ATPases
synthesis Cleistanthin A inhibitor vacuolar H+-ATPase