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Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, The University of Kansas, Lawrence, Malott 4070, U.S.A
E-mail: bblagg@ku.edu
; Fax: +1 (785) 864-5326
; Tel: +1 (785) 864-2288
Med. Chem. Commun., 2010,1, 165-170
DOI:
10.1039/C0MD00063A
Received
30 Apr 2010,
Accepted
17 Jun 2010
First published online
30 Jul 2010
Studies on the natural product, novobiocin, have elucidated specific modifications that increase Hsp90 inhibition. Through diversification of the sugar appendage, coumarin core and benzamide side chain of novobiocin, structurally unique scaffolds have been synthesized. These structural adaptations have produced potent cytotoxic agents, such as KU135, which are prepared more simply than those that contain the noviose sugar. These analogues have been evaluated against two cancer cell lines and demonstrated low micromolar anti-proliferative activity.
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