Bioorganic & Medicinal Chemistry Letters 2011-05-01

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

文献索引：Bioorg. Med. Chem. Lett. 21(9) , 2776-9, (2011)

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摘要

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.