title: [Inhibition of human cytochrome P-450 CYP1A2 by flavonoids: a quantitative structure-activity relationship study ].
abstract: The inhibition activity of 36 flavonoids against CYP1A2 was determined by our previously developed in vitro method. The Comparative Molecular Similarity Indexes Analysis (CoMSJA) approach was used to probe the quantitative relationships between the flavonoids' molecular structural descriptors and their inhibitory activities. A reliable CoMSIA model with the combined electrostatic and hydrophobic fields was derived with the regression coefficient R2 of 0.948 and the cross-validation regression coefficient q2 of 0.630, separately, which is capable of elucidating the quantitative relationship between the 3D structural descriptors of the flavones and their bioactivities. Comparing with flavone, the larger pi-pi conjugated system of alpha-naphthoflavone significantly improved the biologically inhibitory ability. Based on the core structure of the latter, either electropositive substituents or hydrophobic groups at the 6, 3', and 4' ring positions or electronegative counterparts at the 5 ring position, can enhance the inhibitory potency against CYP1 A2 according to the CoMSIA contour maps.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Jian-Kang
authors.initials: JK
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.forename: Hui-Chang
authors.initials: HC
authors.lastname: Bi
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
authors.forename: Bai-dong
authors.initials: BD
authors.lastname: Liu
authors.forename: Hai-bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D005419:Flavonoids; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2