Synthesis of fluorescent derivatives of wortmannin and demethoxyviridin as probes for phosphatidylinositol 3-kinase

José-Luis Giner; Karen A Kehbein; James A Cook; Michele C Smith; Chris J Vlahos; John A Badwey

doi:10.1016/j.bmcl.2006.01.091

Synthesis of fluorescent derivatives of wortmannin and demethoxyviridin as probes for phosphatidylinositol 3-kinase

Bioorg Med Chem Lett. 2006 May 1;16(9):2518-21. doi: 10.1016/j.bmcl.2006.01.091. Epub 2006 Feb 7.

Authors

José-Luis Giner¹, Karen A Kehbein, James A Cook, Michele C Smith, Chris J Vlahos, John A Badwey

Affiliation

¹ Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, USA. jlginer@syr.edu

PMID: 16464575
DOI: 10.1016/j.bmcl.2006.01.091

Abstract

Fluorescent analogs were synthesized of the potent PI 3-kinase inhibitors, wortmannin and demethoxyviridin. The esterification of 11-deacetylwortmannin, 17-hydroxywortmannin, and demethoxyviridin with the fluorescent carboxylic acids NBD-sarcosine and 7-dimethylaminocoumarin-4-acetic acid generated six novel fluorescent esters. Potent inhibition of PI 3-kinase-alpha was observed for the derivatives of 11-desacetylwortmannin and demethoxyviridin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androstadienes / chemical synthesis*
Androstadienes / chemistry
Androstadienes / pharmacology
Androstenes / chemical synthesis*
Androstenes / chemistry
Androstenes / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Fluorescent Dyes / chemical synthesis*
Fluorescent Dyes / chemistry
Fluorescent Dyes / pharmacology
Molecular Conformation
Molecular Probe Techniques
Phosphoinositide-3 Kinase Inhibitors*
Stereoisomerism
Structure-Activity Relationship
Wortmannin

Substances

Androstadienes
Androstenes
Enzyme Inhibitors
Fluorescent Dyes
Phosphoinositide-3 Kinase Inhibitors
demethoxyviridin
Wortmannin