Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 19, Pages 5607-5612Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.08.032
Keywords
Cytochrome P450 3A4; CYP3A4; Pancratistatin; Anticancer agent; Ketoconazole
Categories
Funding
- NSERC
- McMaster University
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Two total syntheses of fully functionalized seco-analogs of the anticancer compound pancratistatin are reported. Structure-activity relationship (SAR) studies identified potent and selective inhibitors of human cytochrome P450 3A4 (CYP3A4) and revealed several core pharmacophoric elements. These studies identify potential roadblocks and will guide the further development of a viable selective clinical pancratistatin derivative. (C) 2009 Elsevier Ltd. All rights reserved.
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