title: Synthesis and aromatase inhibitory activity of novel pyridine-containing isoflavones.
abstract: Aromatase, a cytochrome P450 hemoprotein that is responsible for estrogen biosynthesis by conversion of androgens into estrogens, has been an attractive target in the treatment of hormone-dependent breast cancer. As a result, a number of synthetic steroidal or nonsteroidal aromatase inhibitors have been successfully developed. In addition, there are several classes of natural products that exert potent activities in aromatase inhibition, with the flavonoids being most prominent. Previous studies have exploited flavone and flavanone scaffolds for the development of new aromatase inhibitors. In this paper, we describe the design, synthesis, and biological evaluation of a novel series of 2-(4'-pyridylmethyl)thioisoflavones as the first example of synthetic isoflavone-based aromatase inhibitors.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: John C
authors.initials: JC
authors.lastname: Hackett
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brueggemeier
mesh_terms: D001141:Aromatase / Q000737:chemistry / Q000378:metabolism; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D010920:Placenta / Q000648:ultrastructure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D007529:Isoflavones; D011725:Pyridines; D001141:Aromatase