Synthesis of D- and L-tyrosine-chlorambucil analogs active against breast cancer cell lines.

Abstract

A series of D- and L-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of D- and L-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the D- and L-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line.

• Authors: Caroline Descôteaux, Valérie Leblanc, Kevin Brasseur, Atul Gupta, Eric Asselin, Gervais Bérubé
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 24 Pg. 7388-92 (Dec 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 21051231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Chlorambucil
• Tyrosine
• Receptor, ErbB-2

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Chlorambucil (analogs & derivatives, chemical synthesis, therapeutic use)
• Female
• Humans
• Receptor, ErbB-2 (metabolism)
• Stereoisomerism
• Structure-Activity Relationship
• Tyrosine (chemistry)