Novologues containing, a benzamide side chain manifest anti-proliferative activity against two breast cancer cell lines

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Zhao, Huiping¹  Anyika, Mercy¹  Girgis, Antwan¹  Blagg, Brian S. J.¹ 

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

关键词: Heat shock protein 90;    Hsp90 inhibitors;    Novobiocin analogues;    Breast cancer;   

DOI  :  10.1016/j.bmcl.2014.05.020

来源: Elsevier

【 摘 要 】

Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure-activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Similar to KU-32, we have demonstrated that upon replacement of the acetamide side chain present in KU-32 with a benzamide, this neuroprotective agent was transformed into a scaffold that manifests anti-proliferative activity. To assess structure activity relationships for this new scaffold, a library of benzamide-containing novologues was prepared and evaluated against two breast cancer cell lines. Compound 14a manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation in a concentration-dependent manner. (C) 2014 Published by Elsevier Ltd.

【 授权许可】

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