Evaluating the potential of Vacuolar ATPase inhibitors as anticancer agents and multigram synthesis of the potent salicylihalamide analog saliphenylhalamide

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:18

Article

Lebreton, Sylvain¹  Jaunbergs, Janis¹  Roth, Michael G.^1,2  Ferguson, Deborah A.³  De Brabander, Jef K.^1,2 

[1] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[3] Reata Pharmaceut Inc, Irving, TX 75063 USA

关键词: Natural product;    Total synthesis;    Cancer;    Vacuolar ATPase;   

DOI  :  10.1016/j.bmcl.2008.07.003

来源: Elsevier

【 摘 要 】

The natural product salicylihalamide is a potent inhibitor of the Vacuolar ATPase (V-ATPase), a potential target for antitumor chemotherapy. We generated salicylihalamide- resistant tumor cell lines typified by an overexpansion of lysosomal organelles. We also found that many tumor cell lines upregulate tissuespecific plasmalemmal V-ATPases, and hypothesize that tumors that derive their energy from glycolysis rely on these isoforms to maintain a neutral cytosolic pH. To further validate the potential of V-ATPase inhibitors as leads for cancer chemotherapy, we developed a multigram synthesis of the potent salicylihalamide analog saliphenylhalamide. (C) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

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