3-Arylcoumarin Derivatives Manifest Anti-proliferative Activity through Hsp90 Inhibition

The potential therapeutic benefits associated with Hsp90 modulation for the treatment of cancer and neurodegenerative diseases highlight the importance of identifying novel Hsp90 scaffolds. KU-398, a novobiocin analogue, and silybin were recently identified as new Hsp90 inhibitors. Consequently, a l...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2012-04, Vol.3 (4), p.327-331
Main Authors: Zhao, Huiping, Yan, Bin, Peterson, Laura B, Blagg, Brian S. J
Format: Article
Language:English
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Letter
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Summary:The potential therapeutic benefits associated with Hsp90 modulation for the treatment of cancer and neurodegenerative diseases highlight the importance of identifying novel Hsp90 scaffolds. KU-398, a novobiocin analogue, and silybin were recently identified as new Hsp90 inhibitors. Consequently, a library of 3-arylcoumarin derivatives that incorporated the structural features of KU-398 and silybin was designed, synthesized, and evaluated against two breast cancer cell lines. Western blot analysis confirmed that the resulting 3-arylcoumarin hybrids target the Hsp90 protein folding machinery.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml300018e