Please use this identifier to cite or link to this item: https://doi.org/10.1002/cmdc.201200136
Title: Discovery, Synthesis, and invitro Evaluation of West Nile Virus Protease Inhibitors Based on the 9,10-Dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one Scaffold
Authors: Samanta, S.
Cui, T.
Lam, Y. 
Keywords: Antiviral agents
Bioorganic chemistry
Docking studies
Inhibitors
Proteases
Issue Date: Jul-2012
Citation: Samanta, S., Cui, T., Lam, Y. (2012-07). Discovery, Synthesis, and invitro Evaluation of West Nile Virus Protease Inhibitors Based on the 9,10-Dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one Scaffold. ChemMedChem 7 (7) : 1210-1216. ScholarBank@NUS Repository. https://doi.org/10.1002/cmdc.201200136
Abstract: West Nile virus (WNV), a member of the Flaviviridae family, is a mosquito-borne pathogen that causes a great number of human infections each year. Neither vaccines nor antiviral therapies are currently available for human use. In this study, a WNV NS2B-NS3 protease inhibitor with a 9,10-dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one scaffold was identified by screening a small library of non-peptidic compounds. This initial hit was optimized by solution-phase synthesis and screening of a focused library of compounds bearing this scaffold. This led to the identification of a novel, uncompetitive inhibitor (1a40, IC 50=5.41±0.45μM) of WNV NS2B-NS3 protease. Molecular docking of this chiral compound onto the WNV protease indicates that the Senantiomer of 1a40 appears to interfere with the productive interactions between the NS2B cofactor and the NS3 protease domain; (S)-1a40 is a preferred isomer for inhibition of WNV NS3 protease. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Source Title: ChemMedChem
URI: http://scholarbank.nus.edu.sg/handle/10635/93613
ISSN: 18607179
DOI: 10.1002/cmdc.201200136
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