Impact of absolute stereochemistry on the antiangiogenic and antifungal activities of itraconazole

Wei Shi, Benjamin A. Nacev, Shridhar Bhat, Jun O. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (1a?h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans stereoisomers, especially 1e and 1f, suggest different molecular mechanisms underlying the antiangiogenic and antifungal activities of itraconazole.

Original languageEnglish (US)
Pages (from-to)155-159
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume1
Issue number4
DOIs
StatePublished - Aug 27 2010

Keywords

  • Itraconazole
  • angiogenesis
  • antifungal activity
  • diastereomers
  • stereochemistry

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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