title: QSAR study of natural estrogen-like isoflavonoids and diphenolics from Thai medicinal plants.
abstract: Two species of Thai medicinal plants, Dalbergia parviflora R. (Leguminosae) and Belamcanda chinensis L. (Iridaceae), used traditionally for the regulation of menstrual disorders, have been found to contain a large number of potential estrogen-like compounds. A set of some 55 isolated isoflavonoids and diphenolics showed a wide range of estrogen activity as determined in breast cancer MCF-7 and T47D cell proliferation assays. This set of compounds was studied by means of computational techniques including quantitative structure-activity relationships (QSAR) and molecular modeling. It was found that the estrogenic potencies of the studied compounds depend mainly upon the presence/absence of hydroxyl groups attached to 3' and 5' positions of B ring of the isoflavone scaffold and the inter-atomic distance between the hydroxyl groups attached to the outer terminal positions 7 of A ring and 4' of B ring. In a QSAR model employing ligand-receptor interaction energy descriptors, the LigScore scoring function of Cerius(2) virtual screening module, which describes the receptor affinities of simultaneous binding to estrogenic receptors α and β (ER(α) and ER(β)), led to the best correlation between the observed estrogenic activities and computed descriptors. Consideration of independent binding to ER(α) and ER(β) did not result in statistically significant QSAR models. It was thus concluded that simultaneous and possibly competitive interaction of the compounds with the ER(α) and ER(β) receptors, in which the presence of hydroxyl groups at the abovementioned positions of the isoflavonoids and diphenolics molecular scaffold plays a dominant role, may determine the estrogenic potency of the considered phytochemicals.
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. dwanchai@chula.ac.th
authors.forename: Wanchai
authors.initials: W
authors.lastname: De-Eknamkul
authors.forename: Kaoru
authors.initials: K
authors.lastname: Umehara
authors.forename: Orawan
authors.initials: O
authors.lastname: Monthakantirat
authors.forename: Radovan
authors.initials: R
authors.lastname: Toth
authors.forename: Vladimir
authors.initials: V
authors.lastname: Frecer
authors.forename: Lorena
authors.initials: L
authors.lastname: Knapic
authors.forename: Paolo
authors.initials: P
authors.lastname: Braiuca
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Stanislav
authors.initials: S
authors.lastname: Miertus
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry* / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D035782:Dalbergia / Q000737:chemistry*; D005260:Female; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry / Q000494:pharmacology; D027621:Iridaceae / Q000737:chemistry*; D007529:Isoflavones / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D048789:Phytoestrogens / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D013785:Thailand
chemical_list: D001713:Biphenyl Compounds; D005419:Flavonoids; D017665:Hydroxyl Radical; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; D011960:Receptors, Estrogen; C010574:biphenyl