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 Citations (Scopus)

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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Vacuolar Proton-Translocating ATPases
Tumor Cell Line
Antineoplastic Agents
Tumors
Chemotherapy
Drug Therapy
Glycolysis
Biological Products
Cells
Organelles
Adenosine Triphosphatases
Neoplasms
Protein Isoforms
Up-Regulation
Tissue
saliphenylhalamide

Keywords

  • Cancer
  • Natural product
  • Total synthesis
  • Vacuolar ATPase

ASJC Scopus subject areas

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

Cite this

Evaluating the potential of Vacuolar ATPase inhibitors as anticancer agents and multigram synthesis of the potent salicylihalamide analog saliphenylhalamide. / Lebreton, Sylvain; Jaunbergs, Janis; Roth, Michael G.; Ferguson, Deborah A.; De Brabander, Jef K.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 22, 15.11.2008, p. 5879-5883.

Research output: Contribution to journalArticle

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