Title

Synthesis and Biological Evaluation of Novel Sulfonanilide Compounds as Antiproliferative Agents for Breast Cancer

Document Type

Article

Publication Date

5-1-2008

Publication Title

Journal of Combinatorial Chemistry

Abstract

Combinatorial chemistry approaches facilitate drug discovery processes and result in structural modifications of lead compounds that enhance pharmacological activity, improve pharmacokinetic properties, or reduce unwanted side effects. Epidemiological and animal model studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) can act as chemopreventive agents. The cyclooxygenase-2 (COX-2) inhibitor nimesulide shows anticancer effects in several cancer cell lines via COX-2-dependent and -independent mechanisms. The molecular structure of nimesulide was used as a starting scaffold to design novel sulfonanilide analogs and examine the structural features that contribute to this anticancer effect. A systematic combinatorial chemical approach was used to generate diversely substituted sulfonanilide derivatives that were tested for their effects on the proliferation of human breast cancer cells. Structure–function analysis indicated that the inhibition of cell growth by compounds derived from the novel sulfonanilides required a bulky terminal phenyl ring, a methanesulfonamide, and a hydrophobic carboxamide moiety.

Comments

This work was supported by the National Institutes of Health (NIH) Grant R01 CA73698 (R.W.B.), the USAMRMC Breast Cancer Program Grant W81XWH-08-1-0521, and The Ohio State University Comprehensive Cancer Center Breast Cancer Research Fund.

DOI

10.1021/cc700138n

Volume

10

Issue

3