Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Katherine M. Byrd; Chitra Subramanian; Jacqueline Sanchez; Hashim F. Motiwala; Weiya Liu; Mark S. Cohen; Jeffrey Holzbeierlein; Brian S.J. Blagg

doi:10.1002/chem.201504955

Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Katherine M. Byrd, Chitra Subramanian, Jacqueline Sanchez, Hashim F. Motiwala, Weiya Liu, Mark S. Cohen, Jeffrey Holzbeierlein, Brian S.J. Blagg

Research output: Contribution to journal › Article › peer-review

Abstract

Development of heat shock protein 90 (Hsp90) C-terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti-proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.

Original language	English (US)
Pages (from-to)	6921-6931
Number of pages	11
Journal	Chemistry - A European Journal
Volume	22
Issue number	20
DOIs	https://doi.org/10.1002/chem.201504955
State	Published - May 10 2016
Externally published	Yes

Keywords

antitumor agents
C-terminal inhibitors
Hsp90
luciferase refolding
medicinal chemistry

ASJC Scopus subject areas

Catalysis
Organic Chemistry

Online availability

10.1002/chem.201504955

Library availability

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title = "Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors",

abstract = "Development of heat shock protein 90 (Hsp90) C-terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti-proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 {\AA} apart along with angles of 180°.",

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doi = "10.1002/chem.201504955",

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AU - Byrd, Katherine M.

AU - Subramanian, Chitra

AU - Sanchez, Jacqueline

AU - Motiwala, Hashim F.

AU - Liu, Weiya

AU - Cohen, Mark S.

AU - Holzbeierlein, Jeffrey

AU - Blagg, Brian S.J.

PY - 2016/5/10

Y1 - 2016/5/10

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Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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