Abstract
Naturally occurring furanosteroids such as viridin and wortmannin have long been known as potent inhibitors of the lipid kinase PI-3K. We have been interested in directly accessing analogs of these complex natural products from abundant steroid feedstock materials. In this communication, we describe the synthesis of viridin/wortmannin hybrid molecules from readily available building blocks that function as PI-3K inhibitors and maintain their electrophilic properties. The compounds also show anti-proliferative effects against a breast cancer line.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androstadienes / chemistry
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Androstenes / chemical synthesis
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Androstenes / chemistry*
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Androstenes / toxicity
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Bacteriocins / chemical synthesis
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Bacteriocins / chemistry*
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Bacteriocins / toxicity
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Binding Sites
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Survival / drug effects
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Crystallography, X-Ray
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Female
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Humans
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MCF-7 Cells
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / toxicity
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Protein Structure, Tertiary
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Steroids / chemistry*
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Wortmannin
Substances
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Androstadienes
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Androstenes
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Bacteriocins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Steroids
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viridin
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Wortmannin