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Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole.

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-1h) 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 anti-angiogenic and anti-fungal activities of itraconazole.

SUBMITTER: Shi W

PROVIDER: S-EPMC3165044 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole.

Shi Wei W Nacev Benjamin A BA Bhat Shridhar S Liu Jun O JO

ACS medicinal chemistry letters 20100101 4

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-1h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal ac ...[more]

PMID: 21892383

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