title: Click chemistry to probe Hsp90: Synthesis and evaluation of a series of triazole-containing novobiocin analogues.
abstract: A series of triazole-containing novobiocin analogues has been designed, synthesized and their inhibitory activity determined. These compounds contain a triazole ring in lieu of the amide moiety present in the natural product. The anti-proliferative effects of these compounds were evaluated against two breast cancer cell lines (SKBr-3 and MCF-7), and manifested activities similar to their amide-containing counterparts. In addition, Hsp90-dependent client protein degradation was observed via Western blot analyses, supporting a common mode of Hsp90 inhibition for both structural classes.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, 66045-7582, United States.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Peterson
authors.forename: Brian S J
authors.initials: BS
authors.lastname: Blagg
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D009675:Novobiocin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D014230:Triazoles; D009675:Novobiocin