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Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors.

ABSTRACT: Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued.

SUBMITTER: Zhao J

PROVIDER: S-EPMC4198308 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors.

Zhao Jinbo J Zhao Huiping H Hall Jessica A JA Brown Douglas D Brandes Eileen E Bazzill Joseph J Grogan Patrick T PT Subramanian Chitra C Vielhauer George G Cohen Mark S MS Blagg Brian S J BS

MedChemComm 20140901 9

Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies agai ...[more]

PMID: 25328661

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