Issue 13, 2004
From the journal:

Organic & Biomolecular Chemistry

Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitorwortmannin

Peter Wipf,*a   Daniel J. Minion,a   Robert J. Halter,a   Margareta I. Berggren,b   Caroline B. Ho,c   Gary G. Chiang,c   Lynn Kirkpatrick,d   Robert Abrahamc  and  Garth Powisb  

* Corresponding authors

a Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA

b Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724, USA

c The Burnham Institute, La Jolla, CA 92037, USA

d ProlX Pharmaceuticals, Tucson, AZ 85701, USA

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.

Graphical abstract: Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin

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Article information

DOI
https://doi.org/10.1039/B405431H
Article type
Paper
Submitted
14 Apr 2004
Accepted
11 May 2004
First published
14 Jun 2004

Org. Biomol. Chem., 2004,2, 1911-1920

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Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin

P. Wipf, D. J. Minion, R. J. Halter, M. I. Berggren, C. B. Ho, G. G. Chiang, L. Kirkpatrick, R. Abraham and G. Powis, Org. Biomol. Chem., 2004, 2, 1911 DOI: 10.1039/B405431H

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