Please use this identifier to cite or link to this item:
https://doi.org/10.1021/jm300146f
DC Field | Value | |
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dc.title | Discovery of novel small molecule inhibitors of dengue viral NS2B-NS3 protease using virtual screening and scaffold hopping | |
dc.contributor.author | Deng, J. | |
dc.contributor.author | Li, N. | |
dc.contributor.author | Liu, H. | |
dc.contributor.author | Zuo, Z. | |
dc.contributor.author | Liew, O.W. | |
dc.contributor.author | Xu, W. | |
dc.contributor.author | Chen, G. | |
dc.contributor.author | Tong, X. | |
dc.contributor.author | Tang, W. | |
dc.contributor.author | Zhu, J. | |
dc.contributor.author | Zuo, J. | |
dc.contributor.author | Jiang, H. | |
dc.contributor.author | Yang, C.-G. | |
dc.contributor.author | Li, J. | |
dc.contributor.author | Zhu, W. | |
dc.date.accessioned | 2014-11-26T07:44:14Z | |
dc.date.available | 2014-11-26T07:44:14Z | |
dc.date.issued | 2012-07-26 | |
dc.identifier.citation | Deng, J., Li, N., Liu, H., Zuo, Z., Liew, O.W., Xu, W., Chen, G., Tong, X., Tang, W., Zhu, J., Zuo, J., Jiang, H., Yang, C.-G., Li, J., Zhu, W. (2012-07-26). Discovery of novel small molecule inhibitors of dengue viral NS2B-NS3 protease using virtual screening and scaffold hopping. Journal of Medicinal Chemistry 55 (14) : 6278-6293. ScholarBank@NUS Repository. https://doi.org/10.1021/jm300146f | |
dc.identifier.issn | 00222623 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/109302 | |
dc.description.abstract | By virtual screening, compound 1 was found to be active against NS2B-NS3 protease (IC 50 = 13.12 ± 1.03 μM). Fourteen derivatives (22) of compound 1 were synthesized, leading to the discovery of four new inhibitors with biological activity. In order to expand the chemical diversity of the inhibitors, small-molecule-based scaffold hopping was performed on the basis of the common scaffold of compounds 1 and 22. Twenty-one new compounds (23, 24) containing quinoline (new scaffold) were designed and synthesized. Protease inhibition assays revealed that 12 compounds with the new scaffold are inhibitors of NS2B-NS3 protease. Taken together, 17 new compounds were discovered as NS2B-NS3 protease inhibitors with IC 50 values of 7.46 ± 1.15 to 48.59 ± 3.46 μM, and 8 compounds belonging to two different scaffolds are active to some extent against DENV based on luciferase reporter replicon-based assays. These novel chemical entities could serve as lead structures for discovering therapies against DENV. © 2012 American Chemical Society. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1021/jm300146f | |
dc.source | Scopus | |
dc.type | Article | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1021/jm300146f | |
dc.description.sourcetitle | Journal of Medicinal Chemistry | |
dc.description.volume | 55 | |
dc.description.issue | 14 | |
dc.description.page | 6278-6293 | |
dc.description.coden | JMCMA | |
dc.identifier.isiut | 000306764600003 | |
Appears in Collections: | Staff Publications |
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