Lead optimization of 7-benzyloxy 2-(4'-pyridylmethyl)thio isoflavone aromatase inhibitors.

Bioorg Med Chem

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, 43210, USA.

Published: December 2005

Aromatase, the enzyme responsible for estrogen biosynthesis, is a particularly attractive target in the treatment of hormone-dependent breast cancer. The synthesis and biological evaluation of a series of 2-(4'-pyridylmethyl)thio, 7-alkyl- or aryl-substituted isoflavones as potential aromatase inhibitors are described. The isoflavone derivatives demonstrate IC(50) values from 79 to 553 nM and compete with the endogenous substrate, androstenedione. Data supporting the ability of these analogs to suppress aromatase enzyme activity in the SK-BR-3 breast cancer cell line are also presented.

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http://dx.doi.org/10.1016/j.bmc.2005.07.038DOI Listing

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