Click chemistry to probe Hsp90: Synthesis and evaluation of a series of triazole-containing novobiocin analogues

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 t...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-07, Vol.20 (13), p.3957-3960
Main Authors: Peterson, Laura B., Blagg, Brian S.J.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antiproliferation
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
General aspects
Hsp90
HSP90 Heat-Shock Proteins - antagonists & inhibitors
Humans
Medical sciences
Molecular Structure
Novobiocin
Novobiocin - chemical synthesis
Novobiocin - chemistry
Novobiocin - pharmacology
Pharmacology. Drug treatments
Stereoisomerism
Structure-Activity Relationship
Triazole
Triazoles - chemistry
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.04.140