Diarylheptanoids, new phytoestrogens from the rhizomes of Curcuma comosa:: Isolation, chemical modi. cation and estrogenic activity evaluation

Three new diarylheptanoids, a 1: 2 mixture of (3S)- and (3R)-1-(4-methoxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (13a and 13b) and 1-(4-hydroxyphenyl)-7-phenyl-( 6E)-6-hepten-3- one ( 15), together with two synthetically known diarylheptanoids 1,7-diphenyl-(1E,3E,5E)-1,3,5-triene(9) and 1-(4-hydroxyphenyl)7-phenyl-(4E,6E)-4,6-heptadien-3- one ( 16), and nine known diarylheptanoids, 2, 8, 10 - 12, 14, a 3: 1 mixture of 17a and 17b, and 18, were isolated from the rhizomes of Curcuma comosa Roxb. The absolute stereochemistry of the isolated compounds has also been determined using the modified Mosher's method. The isolated compounds and the chemically modified analogues were evaluated for their estrogenic-like transcriptional activity using RT-PCR in HeLa cell line. Some of the isolated diarylheptanoids and their modified analogues exhibited estrogenic activity comparable to or higher than that of the phytoestrogen genistein. Based on the transcriptional activation of both estrogenic targets, Bcl-xL and ER beta gene expression, the structural features for a diarylheptanoid to exhibit high estrogenic activity are the presence of an phenolic function conjugated with the aromatic ring at the 7-position, a keto group at the 3-position, and a phenolic hydroxyl group at the p-position of the aromatic ring attached to the 1- position of the heptyl chain. (c) 2008 Elsevier Ltd. All rights reserved.