title: Synthesis and bioevaluation of heterocyclic derivatives of Cleistanthin-A.
abstract: The vacuolar H(+)-ATPase (V-ATPase) was proposed as a key target for new strategies in cancer treatment recently. We have synthesized a novel class of derivatives of Cleistanthin-A bearing heterocyclic moieties. Most of these compounds displayed potent antiproliferative effects on four cancer cells at submicromolar concentration, and they have no cytotoxicity on normal WRL-68 cells at 200 nM. The most potent compound 3a has been shown to inhibit the activity of vacuolar H(+)-ATPase at submicromolar concentration, and it could also significantly decrease the cytosolic pH values in HepG2 cells. The current findings provide valuable insights for future development of novel V-ATPase inhibitors as anticancer agents.
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Lu
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. Electronic address: zhulili65@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; 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