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ID: ALA3596156

Journal: Bioorg Med Chem

Title: Synthesis and bioevaluation of heterocyclic derivatives of Cleistanthin-A.

Authors: Zhao Y, Zhang R, Lu Y, Ma J, Zhu L.

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.

CiteXplore: 26059594

DOI: 10.1016/j.bmc.2015.05.033