Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents.
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.
Sekiguchi
Hironori
H
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Muranaka
Kazuhiro
K
Osada
Akiko
A
Ichikawa
Satoshi
S
Matsuda
Akira
A
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
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D003300:Copper; D000225:Adenine