title: Synthesis and evaluation of coumermycin A1 analogues that inhibit the Hsp90 protein folding machinery.
abstract: [structure: see text] The coumarin antibiotics are not only potent inhibitors of DNA gyrase but also represent the most effective C-terminal inhibitors of 90 kDa heat shock proteins (Hsp90) reported thus far. In contrast to the N-terminal ATP-binding site, little is known about the Hsp90 C-terminus. In addition, very limited structure-activity relationships exist between this class of natural products and Hsp90. In this letter, the syntheses of dimeric coumarin analogues are presented along with their inhibitory values in breast cancer cell lines.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7563, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Burlison
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
mesh_terms: D049933:Aminocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D017510:Protein Folding; D014407:Tumor Cells, Cultured
chemical_list: D049933:Aminocoumarins; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; C004628:coumermycin