Τίτλος:
Ester and carbamate ester derivatives of Biochanin A: Synthesis and in vitro evaluation of estrogenic and antiproliferative activities
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2012 Elsevier Ltd. All rights reserved.
Συγγραφείς:
Fokialakis, N.
Alexi, X.
Aligiannis, N.
Siriani, D.
Meligova, A.K.
Pratsinis, H.
Mitakou, S.
Alexis, M.N.
Περιοδικό:
BIOORGANIC AND MEDICINAL CHEMISTRY
Λέξεις-κλειδιά:
1,3,5 tris(4 hydroxyphenyl) 4 propylpyrazole; 5 hydroxy 3 (4 methoxyphenyl) 4 oxo 4h chromen 7 yl 2 bromoacetate; 5 hydroxy 3 (4 methoxyphenyl) 4 oxo 4h chromen 7 yl 2 bromoethylcarbamate; 5 hydroxy 3 (4 methoxyphenyl) 4 oxo 4h chromen 7 yl 2 chloroacetate; 5 hydroxy 3 (4 methoxyphenyl) 4 oxo 4h chromen 7 yl 2 chloroethylcarbamate; 5 hydroxy 3 (4 methoxyphenyl) 4 oxo 4h chromen 7 yl 2 undecylcarbamate; 5 hydroxy 3 (methoxyphenyl) 4 oxo 4h chromen 7 yl 2 chloroacetate; antineoplastic agent; biochanin A; diarylpropionitrile; estradiol; estrogen receptor alpha; estrogen receptor beta; hormone receptor stimulating agent; methylpiperidino pyrazole; unclassified drug, antiproliferative activity; article; binding affinity; cancer cell culture; cancer inhibition; cell proliferation; controlled study; drug effect; drug mechanism; drug receptor binding; drug stability; drug synthesis; estrogen activity; gene induction; human; human cell; IC 50; protein expression; structure activity relation, Antineoplastic Agents; Carbamates; Cell Line, Tumor; Cell Proliferation; Esters; Genistein; Humans; Trifolium, Trifolium pratense
DOI:
10.1016/j.bmc.2012.03.012
