title: Lead optimization of 7-benzyloxy 2-(4'-pyridylmethyl)thio isoflavone aromatase inhibitors.
abstract: Aromatase, the enzyme responsible for estrogen biosynthesis, is a particularly attractive target in the treatment of hormone-dependent breast cancer. The synthesis and biological evaluation of a series of 2-(4'-pyridylmethyl)thio, 7-alkyl- or aryl-substituted isoflavones as potential aromatase inhibitors are described. The isoflavone derivatives demonstrate IC(50) values from 79 to 553 nM and compete with the endogenous substrate, androstenedione. Data supporting the ability of these analogs to suppress aromatase enzyme activity in the SK-BR-3 breast cancer cell line are also presented.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, 43210, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.forename: John C
authors.initials: JC
authors.lastname: Hackett
authors.forename: Edgar S
authors.initials: ES
authors.lastname: Díaz-Cruz
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Robert W
authors.initials: RW
authors.lastname: Brueggemeier
mesh_terms: D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D047072:Aromatase Inhibitors; D007529:Isoflavones; D001141:Aromatase