Studies on the Novel Anticancer Agents Metabolically Formed from 17- Beta-Estradiol

摘要

By using NMR and mass spectrometric analyses, we determined the structures of Xl and X2, two representative nonpolar estrogen metabolites, which were metabolically formed following multiple large-scale incubations of 17 beta- estradiol with human CYP3A4 and NADPH. Both Xl and X2 were unequivocally identified to be the dimers of l7 beta-estradiol, connected together through a diaryl ether bond between a phenolic oxygen atom of one l7 beta-estradiol molecule and the 2- or 4-position aromatic carbon of another estrogen. This is the first report for a novel class of the nonpolar l7 beta-estradiol dimers that are formed from l7 beta- estradiol by human Cyp isoforms in the presence of NADPH as a cofactor.