dc.contributor.author | Li, Kelin | |
dc.contributor.author | Frankowski, Kevin J. | |
dc.contributor.author | Belon, Craig A. | |
dc.contributor.author | Neuenswander, Benjamin | |
dc.contributor.author | Ndjomou, Jean | |
dc.contributor.author | Hanson, Alicia M. | |
dc.contributor.author | Shanahan, Matthew A. | |
dc.contributor.author | Schoenen, Frank J. | |
dc.contributor.author | Blagg, Brian S. J. | |
dc.contributor.author | Aubé, Jeffrey | |
dc.contributor.author | Frick, David N. | |
dc.date.accessioned | 2017-04-06T17:20:13Z | |
dc.date.available | 2017-04-06T17:20:13Z | |
dc.date.issued | 2012-04-12 | |
dc.identifier.citation | Li, K., Frankowski, K. J., Belon, C. A., Neuenswander, B., Ndjomou, J., Hanson, A. M., … Frick, D. N. (2012). Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S and Primuline. Journal of Medicinal Chemistry, 55(7), 3319–3330. http://doi.org/10.1021/jm300021v | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23594 | |
dc.description.abstract | A screen for hepatitis C virus (HCV) NS3 helicase inhibitors revealed that the commercial dye thioflavine S was the most potent inhibitor of NS3-catalyzed DNA and RNA unwinding in the 827-compound National Cancer Institute Mechanistic Set. Thioflavine S and the related dye primuline were separated here into their pure components, all of which were oligomers of substituted benzothiazoles. The most potent compound (P4), a benzothiazole tetramer, inhibited unwinding >50% at 2±1 μM, inhibited the subgenomic HCV replicon at 10 μM, and was not toxic at 100 μM. Because P4 also interacted with DNA, more specific analogs were synthesized from the abundant dimeric component of primuline. Some of the 29 analogs prepared retained ability to inhibit HCV helicase but did not appear to interact with DNA. The most potent of these specific helicase inhibitors (compound 17) was active against the replicon and inhibited the helicase more than 50% at 2.6±1 μM. | 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/jm300021v. | en_US |
dc.subject | Hepatitis C virus | en_US |
dc.subject | NS3 | en_US |
dc.subject | Helicase | en_US |
dc.subject | Protease | en_US |
dc.subject | ATPase | en_US |
dc.subject | Benzothiazoles | en_US |
dc.title | Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S Primuline | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Li, Kelin | |
kusw.kuauthor | Frankowski, Kevin J. | |
kusw.kuauthor | Nueuenswander, Ben | |
kusw.kuauthor | Schoenen, Frank J. | |
kusw.kuauthor | Blagg, Brian S. J. | |
kusw.kuauthor | Aub, Jeffrey | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1021/jm300021v | 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 | |