Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents

The PU-H58-dimers were designed as potential Hsp90 inhibitors and efficiently synthesized by the copper-catalyzed alkyne azide coupling (CuAAC) and their biological properties including binding affinity to the N-terminal domain of Hsp90, cytotoxicity, and client degradation activity were evaluated....

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2010-08, Vol.18 (15), p.5732-5737
Main Authors: Sekiguchi, Hironori, Muranaka, Kazuhiro, Osada, Akiko, Ichikawa, Satoshi, Matsuda, Akira
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - chemical synthesis
Adenine - toxicity
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - toxicity
Antitumor agent
Biological and medical sciences
Catalysis
Cell Line, Tumor
Copper - chemistry
Copper-catalyzed alkyne azide coupling
Dimerization
General aspects
Hsp90
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - metabolism
Humans
Medical sciences
Pharmacology. Drug treatments
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The PU-H58-dimers were designed as potential Hsp90 inhibitors and efficiently synthesized by the copper-catalyzed alkyne azide coupling (CuAAC) and their biological properties including binding affinity to the N-terminal domain of Hsp90, cytotoxicity, and client degradation activity were evaluated. 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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2010.05.075