title: Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents.
abstract: The PU-H58-dimers 13a-15b were efficiently synthesized and their biological properties were evaluated. The copper-catalyzed alkyne azide coupling was effective in simultaneously linking three components via a triazole formation to afford the target dimers. These synthesized dimers exhibited binding affinity to the N-terminal domain of Hsp90, cytotoxicity, and client degradation activity although these activities were comparative or weak comparable with that of the parent compound.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Sekiguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Muranaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Osada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002384:Catalysis; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D019281:Dimerization; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D003300:Copper; D000225:Adenine