title: Optimization of the aromatase inhibitory activities of pyridylthiazole analogues of resveratrol.
abstract: Aromatase is an established target not only for breast cancer chemotherapy, but also for breast cancer chemoprevention. The moderate and non-selective aromatase inhibitory activity of resveratrol (1) was improved about 100-fold by replacement of the ethylenic bridge with a thiadiazole and the phenyl rings with pyridines (e.g., compound 3). The aromatase inhibitory activity was enhanced over 6000-fold by using a 1,3-thiazole as the central ring and modifying the substituents on the 'A' ring to target the Met374 residue of aromatase. On the other hand, targeting the hydroxyl group of Thr310 by a hydrogen-bond acceptor on the 'B' ring did not improve the aromatase inhibitory activity.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Abdelrahman S
authors.initials: AS
authors.lastname: Mayhoub
authors.forename: Laura
authors.initials: L
authors.lastname: Marler
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: Mark
authors.initials: M
authors.lastname: Cushman
mesh_terms: D001141:Aromatase / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D057075:Enzyme Assays; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D047072:Aromatase Inhibitors; D013267:Stilbenes; D013844:Thiazoles; D001141:Aromatase; D000077185:Resveratrol