title: Synthesis and characterization of azole isoflavone inhibitors of aromatase.
abstract: The synthesis and biological evaluation of a series of 2-azole and 2-thioazole isoflavones as potential aromatase inhibitors are described. Differences in inhibitory activity of triazole and imidazole inhibitors are rationalized with density functional theory to expose a key difference in the electronic structure of these molecules. In addition, difference binding spectra of inhibitors to immunoaffinity-purified aromatase produces classical Type II spectra consistent with coordination of the nitrogen lone pair electrons to the aromatase P450 heme.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12th Avenue, Columbus, OH 43210, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Hackett
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brueggemeier
mesh_terms: D000735:Androstenedione / Q000494:pharmacology; D001141:Aromatase / Q000737:chemistry; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis / Q000494:pharmacology; D004583:Electrons; D005260:Female; D006418:Heme; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes; D008958:Models, Molecular; D010920:Placenta; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D001393:Azoles; D007529:Isoflavones; D000735:Androstenedione; D006418:Heme; D001141:Aromatase