Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents

Zhao, Huiping; Donnelly, Alison C.; Kusuma, Bhaskar Reddy; Brandt, Gary E. L.; Brown, Douglas; Rajewski, Roger A.; Bielhauer, George; Holzbeierlein, Jeffery M.; Cohen, Mark S.; Blagg, Brian S. J.

dc.contributor.author	Zhao, Huiping
dc.contributor.author	Donnelly, Alison C.
dc.contributor.author	Kusuma, Bhaskar Reddy
dc.contributor.author	Brandt, Gary E. L.
dc.contributor.author	Brown, Douglas
dc.contributor.author	Rajewski, Roger A.
dc.contributor.author	Bielhauer, George
dc.contributor.author	Holzbeierlein, Jeffery M.
dc.contributor.author	Cohen, Mark S.
dc.contributor.author	Blagg, Brian S. J.
dc.date.accessioned	2017-04-06T16:58:07Z
dc.date.available	2017-04-06T16:58:07Z
dc.date.issued	2011-06-09
dc.identifier.citation	Zhao, H., Donnelly, A. C., Kusuma, B. R., Brandt, G. E. L., Brown, D., Rajewski, R. A., … Blagg, B. S. J. (2011). Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents. Journal of Medicinal Chemistry, 54(11), 3839–3853. http://doi.org/10.1021/jm200148p	en_US
dc.identifier.uri	http://hdl.handle.net/1808/23591
dc.description.abstract	Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition.	en_US
dc.publisher	American Chemical Society	en_US
dc.rights	This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm200148p.	en_US
dc.title	Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents	en_US
dc.type	Article	en_US
kusw.kuauthor	Zhao, Huiping
kusw.kuauthor	Donnelly, Alison C.
kusw.kuauthor	Kusuma, Bhaskar Reddy
kusw.kuauthor	Brandt, Gary E. L.
kusw.kuauthor	Brown, Douglas
kusw.kuauthor	Rajewski, Roger A.
kusw.kuauthor	Vielhaur, George
kusw.kuauthor	Holzbeirerlein, Jeffrey
kusw.kuauthor	Cohen, Mark S.
kusw.kuauthor	Blagg, Brian S. J.
dc.identifier.doi	10.1021/jm200148p	en_US
kusw.oaversion	Scholarly/refereed, author accepted manuscript	en_US
kusw.oapolicy	This item meets KU Open Access policy criteria.	en_US
dc.rights.accessrights	openAccess

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