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Title: New 1-phenyl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides inhibit hepatitis C virus replication via suppression of cyclooxygenase-2
Authors: Manvar, Dinesh ×
Pelliccia, Sveva
La Regina, Giuseppe
Famiglini, Valeria
Coluccia, Antonio
Ruggieri, Anna
Anticoli, Simona
Lee, Jin-Ching
Basu, Amartya
Cevik, Ozge
Nencioni, Lucia
Palamara, Anna Teresa
Zamperini, Claudio
Botta, Maurizio
Neyts, Johan
Leyssen, Pieter
Kaushik-Basu, Neerja
Silvestri, Romano #
Issue Date: Jan-2015
Series Title: European Journal of Medicinal Chemistry vol:90 pages:497-506
Article number: S0223-5234(14)01074-5
Abstract: We report here the synthesis and mechanism of inhibition of pyrazolecarboxamide derivatives as a new class of HCV inhibitors. Compounds 6, 7, 8 and 16 inhibited the subgenomic HCV replicon 1b genotype at EC50 values between 5 and 8 μM and displayed an even higher potency against the infectious Jc1 HCV 2a genotype. Compound 6 exhibited an EC50 of 6.7 μM and selectivity index of 23 against HCV 1b, and reduced the RNA copies of the infectious Jc1 chimeric 2a clone by 82% at 7 μM. Evaluation of the mode of anti-HCV activity of 6 revealed that it suppressed HCV-induced COX-2 mRNA and protein expression, displaying an IC50 of 3.2 μM in COX-2 promoter-linked luciferase reporter assay. Conversely, the anti-HCV activity of 6 was abrogated upon over-expression of COX-2. These findings suggest that 6 as a representative of these pyrazolecarboxamides function as anti-HCV agents via targeting COX-2 at both the transcription and translation levels.
URI: 
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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