Abstract |
A series of viridin analogs was prepared from wortmannin by nucleophilic ring opening at C(20) and evaluated against the signaling kinases PI-3-kinase and mTOR. Several subnanomolar enzyme inhibitors with orders of magnitude selectivity for PI-3-kinase and strong cytotoxic activity against four cancer cell lines were identified. Among the ten most promising derivatives, six demonstrated lower liver toxicity and greater promise for inhibition of tumor cell growth than the lead structure wortmannin.
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Authors | Peter Wipf, Daniel J Minion, Robert J Halter, Margareta I Berggren, Caroline B Ho, Gary G Chiang, Lynn Kirkpatrick, Robert Abraham, Garth Powis |
Journal | Organic & biomolecular chemistry
(Org Biomol Chem)
Vol. 2
Issue 13
Pg. 1911-20
(Jul 07 2004)
ISSN: 1477-0520 [Print] England |
PMID | 15227545
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Androstadienes
- Androstenes
- Bacteriocins
- Phosphatidylinositols
- Phosphoinositide-3 Kinase Inhibitors
- Protein Kinase Inhibitors
- viridin
- Wortmannin
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Topics |
- Alkylation
- Androstadienes
(chemistry, pharmacology)
- Androstenes
(chemical synthesis, chemistry, pharmacology, toxicity)
- Bacteriocins
(chemical synthesis, chemistry, pharmacology, toxicity)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Humans
- Inhibitory Concentration 50
- Molecular Structure
- Phosphatidylinositols
(chemistry, metabolism)
- Phosphoinositide-3 Kinase Inhibitors
- Protein Kinase Inhibitors
(chemical synthesis, chemistry, pharmacology)
- Substrate Specificity
- Wortmannin
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