Document Type

Article

Publication Date

6-2-2005

Publication Title

Bioorganic & Medicinal Chemistry

Abstract

The synthesis and biological evaluation of a series of 2-azole and 2-thioazole isoflavones as potential aromatase inhibitors are described. Differences in inhibitory activity of triazole and imidazole inhibitors are rationalized with density functional theory to expose a key difference in the electronic structure of these molecules. In addition, difference binding spectra of inhibitors to immunoaffinity-purified aromatase produces classical Type II spectra consistent with coordination of the nitrogen lone pair electrons to the aromatase P450 heme.

Comments

This research was supported by a USAMRMC Breast Cancer Program grants Pre-doctoral Fellowship DMAD17-02-1-0529 (J.C.H.), DMAD17-99-1-9342 (Y.W.K.), and Idea Grant DMAD-17-00-1-0388 (R.W.B.). The authors are indebted to the Ohio Supercomputer Center for computational resources.

DOI

10.1016/j.bmc.2005.03.050

Version

Postprint

Volume

13

Issue

12

Included in

Chemistry Commons

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