Thapsigargin analogues for targeting programmed death of androgen-independent prostate cancer cells

S. Brøgger Christensen, Annette Andersen, Hasse Kromann, Marek Treiman, Bertrand Tombal, Sam Denmeade, John T. Isaacs

Research output: Contribution to journalArticlepeer-review

Abstract

A number of analogues of thapsigargin, a selective inhibitor of the sarco-endoplasmic reticulum Ca2+-ATPases have been synthesized. In all of the prepared analogues the butanoyl residue at O-8 has been replaced with a residue containing an aromatic amine. The amine can be used as an anchoring point for attaching a peptide group sensitive to the proteolytic enzyme, prostate specific antigen, secreted by prostate cancer cells. Like thapsigargin, the analogues are capable of elevating the cytoplasmic Ca2+ concentration approximately sevenfold when tested at effective cytotoxic doses. The analogues in which the 8-O-butanoyl group has been replaced with 3-(4-aminophenyl)propanoyl or 4-aminocinnamoyl were found potently to induce programmed cell death of the prostate cancer cells. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1273-1280
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume7
Issue number7
DOIs
StatePublished - Jul 1999

Keywords

  • Apoptosis
  • Prodrug
  • Prostate cancer
  • Prostate-specific antigen
  • Thapsigargin

ASJC Scopus subject areas

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

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