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dc.contributor.authorLai, Huiguo
dc.contributor.authorDou, Dengfeng
dc.contributor.authorAravapalli, Sridhar
dc.contributor.authorTeramoto, Tadahisa
dc.contributor.authorLushington, Gerald H.
dc.contributor.authorMwania, Tom M.
dc.contributor.authorAlliston, Kevin R.
dc.contributor.authorEichhorn, David M.
dc.contributor.authorPadmanabhan, Radhakrishnan
dc.contributor.authorGroutas, William C.
dc.date.accessioned2013-04-15T18:01:13Z
dc.date.available2013-04-15T18:01:13Z
dc.date.issued2013-01
dc.identifier.citationLai, Huiguo; Dou, Dengfeng; Aravapalli, Sridhar; Teramoto, Tadahisa; Lushington, Gerald H.; Mwania, Tom M.; Alliston, Kevin R.; Eichhorn, David M.; Padmanabhan, Radhakrishnan; Groutas, William C. 2013. Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases. Bioorganic & Medicinal Chemistry, v.21 no.1 pp.102-113en_US
dc.identifier.issn0968-0896
dc.identifier.otherWOS:000312275500009
dc.identifier.urihttp://dx.doi.org/10.1016/j.bmc.2012.10.058
dc.identifier.urihttp://hdl.handle.net/10057/5605
dc.descriptionClick on the DOI link to access the article (may not be free.)en_US
dc.description.abstract1,2-Benzisothiazol-3(2H)-ones and 1,3,4-oxadiazoles individually have recently attracted considerable interest in drug discovery, including as antibacterial and antifungal agents. In this study, a series of functionalized 1,2-benzisothiazol-3(2H)-one-1,3,4-oxadiazole hybrid derivatives were synthesized and subsequently screened against Dengue and West Nile virus proteases. Ten out of twenty-four compounds showed greater than 50% inhibition against DENV2 and WNV proteases ([I] = 10 mu M). The IC50 values of compound 7n against DENV2 and WNV NS2B/NS3 were found to be 3.75 +/- 0.06 and 4.22 +/- 0.07 mu M, respectively. The kinetics data support a competitive mode of inhibition by compound 7n. Molecular modeling studies were performed to delineate the putative binding mode of this series of compounds. This study reveals that the hybrid series arising from the linking of the two scaffolds provides a suitable platform for conducting a hit-to-lead optimization campaign via iterative structure-activity relationship studies, in vitro screening and X-ray crystallography.en_US
dc.language.isoen_USen_US
dc.publisherPERGAMON-ELSEVIER SCIENCE LTDen_US
dc.relation.ispartofseriesBioorganic & Medicinal Chemistry;v.21 no.1
dc.subject1,2-Benzisothiazol-3(2H)-onesen_US
dc.subject1,3,4-Oxadiazolesen_US
dc.subjectDengue virus proteaseen_US
dc.subjectWest Nile virus proteaseen_US
dc.titleDesign, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteasesen_US
dc.typeArticleen_US
dc.description.versionPeer revieweden
dc.rights.holderCopyright © 2013, Elsevieren


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