title: Estrogenic activities of isoflavones and flavones and their structure-activity relationships.
abstract: In this study, we assessed the relationships between the structure and estrogenicity of flavonoid derivatives. We evaluated estrogenicity via yeast transactivation assays, E-screen assays, and ER binding assays. Genistein and coumestrol in the yeast transactivation assay and biochanin A, genistein, and equol in the E-screen assay, have been shown to have profound estrogenic activities. Flavonoids, with the exception of biochanin A and daidzein, exhibit more profound selectivity for ER beta than for ER alpha. We compared several flavonoids in terms of estrogenicity, as well as relatively small structural differences including the position of the phenol ring and hydroxy groups, the substitution of hydroxy groups or methoxy groups, the opening of the phenol ring; glycitein vs. 4',6,7-trihydroxyisoflavone, biochanin A vs. genistein, apigenin vs. genistein, 7,4'-dihydroxyflavone vs. isoliquiritigenin. A quantitative structure-activity relationship study design was utilized to develop model equations for the estrogenic activities of flavonoid derivatives. The prediction of estrogenicity with regard to ER alpha shows a positive correlation with MW and AlogP, and a negative correlation with Apol and Area (r2 = 0.89 and q2 = 0.83). The prediction of estrogenicity with regard to ER beta reveals a positive correlation with the AlogP and Hbond acceptors, and a negative correlation with RadOfGyration (r2 = 0.77 and q2 = 0.72).
authors: Food Function Research Group, Korea Food Research Institute, Gyeonggi-do, Republic of Korea.
authors: Sun Young
authors: SY
authors: Choi
authors: Tae Youl
authors: TY
authors: Ha
authors: Ji Yun
authors: JY
authors: Ahn
authors: Sung Ran
authors: SR
authors: Kim
authors: Kyung Sun
authors: KS
authors: Kang
authors: In Kyeong
authors: IK
authors: Hwang
authors: Suna
authors: S
authors: Kim
mesh_terms: D001681:Biological Assay; D047309:Flavones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D048789:Phytoestrogens / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010946:Plants, Medicinal; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D047309:Flavones; D007529:Isoflavones; D048789:Phytoestrogens