Ester and carbamate ester derivatives of Biochanin A: synthesis and in vitro evaluation of estrogenic and antiproliferative activities.

Abstract

Biochanin A (BCA), a major isoflavone in red clover and many other legumes, has been reported to display estrogenic as well as cancer chemopreventive properties. Ingested BCA is known to display low bioavailability due to poor solubility, extensive metabolism and rapid clearance. Esters of bioactive isoflavones are known to increase metabolic stability and bioavailability following local rather than systemic administration. We synthesized BCA from phloroglucinol and p-methoxy-phenylacetic acid by a Friedel-Crafts reaction and cyclization. We also synthesized esters (1, 3) and carbamate esters (2, 4, 5) at position 7 of BCA using short aliphatic chains bearing a chlorine (1, 2) or a bromine atom (3, 4) or long aliphatic chains without such atoms (5). We tested the estrogenic and antiproliferative activities of 1-5 and BCA using human breast and endometrial adenocarcinoma cells. We found that 5 affects MCF-7 and Ishikawa cells in a manner providing for induction of gene expression to a level similar to 17β-estradiol and BCA but, unlike both of the latter, for suppression of cell proliferation as well. In addition, 5 appeared to display higher stability compared to 1-4 and BCA in both MCF-7 and Ishikawa cells. The inference is that 5 may represent a safer than BCA alternative to hormone replacement therapy.

• Authors: Nikolas Fokialakis, Xanthippi Alexi, Nektarios Aligiannis, Despina Siriani, Aggeliki K Meligova, Harris Pratsinis, Sofia Mitakou, Michael N Alexis
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 20 Issue 9 Pg. 2962-70 (May 01 2012) ISSN: 1464-3391 [Electronic] England
• PMID: 22464681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Carbamates
• Esters
• Genistein
• biochanin A

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carbamates (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Esters
• Genistein (chemical synthesis, chemistry, pharmacology)
• Humans
• Trifolium (chemistry)