Synthesis and evaluation of C2 functionalized analogs of the α-tubulin-binding natural product pironetin

David S. Huang, Henry L. Wong, Gunda I. Georg

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Pironetin is an α-tubulin-binding natural product with potent antiproliferative activity against several cancer cell lines that inhibits cell division by forming a covalent adduct with α-tubulin via a Michael addition into the natural product's α,β-unsaturated lactone. We designed and prepared analogs carrying electron-withdrawing groups at the α-position (C2) of the α,β-unsaturated lactone with the goal to generate potent and selective binding analogs. We prepared derivatives containing halogens, a phenyl, and a methyl group at the C2 position to evaluate the structure-activity relationship at this position. Testing of the analogs in ovarian cancer cell lines demonstrated 100–1000-fold decreased antiproliferative activity.

Original languageEnglish (US)
Pages (from-to)2789-2793
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume28
Issue number16
DOIs
StatePublished - Sep 1 2018

Keywords

  • Cytotoxicity
  • Pironetin
  • Structure-activity
  • Synthesis
  • Tubulin

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