Synthesis and in Vitro Evaluation of New Wortmannin Esters: Potent Inhibitors of Phosphatidylinositol 3-Kinase
- 1 January 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 39 (25) , 5021-5024
- https://doi.org/10.1021/jm960283z
Abstract
New C-11 esters of the fermentation product wortmannin have been synthesized, with some of them further derivatized at C-17. The new esters show greater inhibition of isolated phosphatidylinositol 3-kinase and increased cell cytotoxicity in a rapidly proliferating leukemia cell line, when compared to wortmannin. Reduction of the C-17 ketone caused a slight increase in activity, while acylation of this new alcohol caused severe loss of activity. With their increased activity, the new C-11 esters may be good candidates to explore the in vivo antitumor effects of phosphatidylinositol 3-kinase inhibitors.Keywords
This publication has 8 references indexed in Scilit:
- A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).Journal of Biological Chemistry, 1994
- Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells.Journal of Biological Chemistry, 1993
- Signal transduction in neutrophil activation Phosphatidylinositol 3‐kinase is stimulated without tyrosine phosphorylationFEBS Letters, 1992
- Phosphatidylinositol 3′-kinase is activated by association with IRS-1 during insulin stimulation.The EMBO Journal, 1992
- The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinaseNature, 1989
- Polyphosphoinositides Produced by Phosphatidylinositol 3-Kinase Are Poor Substrates for Phospholipases C from Rat Liver and Bovine BrainJournal of Biological Chemistry, 1989
- Isolation and purification of a hemorrhagic factor (wortmannin) from Fusarium oxysporum (N17B)Applied and Environmental Microbiology, 1988
- Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformationNature, 1985