title: 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.affiliation: Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Panepistimiopolis, 157 71 Athens, Greece.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Fokialakis
authors.forename: Xanthippi
authors.initials: X
authors.lastname: Alexi
authors.forename: Nektarios
authors.initials: N
authors.lastname: Aligiannis
authors.forename: Despina
authors.initials: D
authors.lastname: Siriani
authors.forename: Aggeliki K
authors.initials: AK
authors.lastname: Meligova
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Sofia
authors.initials: S
authors.lastname: Mitakou
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004952:Esters; D019833:Genistein / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D029921:Trifolium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D004952:Esters; D019833:Genistein; C004541:biochanin A