Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase.
Sandra Gemma, Stefania Butini, Giuseppe Campiani, Margherita Brindisi, Samantha Zanoli, Maria Pia Romano, Pierangela Tripaldi, Luisa Savini, Isabella Fiorini, Giuseppe Borrelli, Ettore Novellino, Giovanni Maga
Index: Bioorg. Med. Chem. Lett. 21(9) , 2776-9, (2011)
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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.