1. Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase.
- Author
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Gemma S, Butini S, Campiani G, Brindisi M, Zanoli S, Romano MP, Tripaldi P, Savini L, Fiorini I, Borrelli G, Novellino E, and Maga G
- Subjects
- Binding, Competitive drug effects, Hydrazines chemical synthesis, Protein Binding, Pyrazines chemical synthesis, Quinolines chemical synthesis, Drug Discovery, Hepacivirus enzymology, Hydrazines chemistry, Hydrazines pharmacology, Pyrazines chemistry, Pyrazines pharmacology, Quinolines chemistry, Quinolines pharmacology, Viral Nonstructural Proteins antagonists & inhibitors
- Abstract
Among the enzymes involved in the life cycle of HCV, the non-structural protein NS3, with its double function of protease and NTPase/helicase, is essential for the virus replication. Exploiting our previous knowledge in the development of nucleotide-mimicking NS3 helicase (NS3h) inhibitors endowed with key structural and electronic features necessary for an optimal ligand-enzyme interaction, we developed the tetrahydroacridinyl derivative 3a as the most potent NS3h competitive inhibitor reported to date (HCV NS3h K(i)=20 nM)., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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