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

Sylvain Lebreton, Janis Jaunbergs, Michael G. Roth, Deborah A. Ferguson, Jef K. De Brabander

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 tissue-specific 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.

Original languageEnglish (US)
Pages (from-to)5879-5883
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number22
DOIs
StatePublished - Nov 15 2008

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Keywords

  • Cancer
  • Natural product
  • Total synthesis
  • Vacuolar ATPase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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