Novel 6-Aminoquinazolinone Derivatives as Potential Cross GT1-4 HCV NS5B Inhibitors
Tamer Nasr,
Ahmed M. Aboshanab,
George Mpekoulis,
Antonios Drakopoulos,
Niki Vassilaki,
Grigoris Zoidis,
Khaled A. M. Abouzid,
Wafaa Zaghary
Affiliations
Tamer Nasr
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
Ahmed M. Aboshanab
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
George Mpekoulis
Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
Antonios Drakopoulos
Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
Niki Vassilaki
Molecular Virology Laboratory, Hellenic Pasteur Institute, 11521 Athens, Greece
Grigoris Zoidis
Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Khaled A. M. Abouzid
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt
Wafaa Zaghary
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain-Helwan, Cairo 11795, Egypt
Chronic hepatitis C virus (HCV) infections are a worldwide medical problem responsible for diverse types of liver diseases. The NS5B polymerase enzyme has become a very interesting target for the development of anti-HCV drugs owing to its fundamental role in viral replication. Here we report the synthesis of a novel series of 1-substituted phenyl-4(1H)-quinazolinone and 2-methyl-1-substituted phenyl-4(1H)-quinazolinone derivatives and evaluate their activity against HCV in HCV subgenomic replicon assays. The biological data revealed that compound 11a showed the highest activity against HCV GT1b at a micromolar concentration (EC50 = 0.984 µM) followed by compound 11b (EC50 = 1.38 µM). Both compounds 11a and 11b had high selectivity indices (SI = CC50/EC50), 160.71 and 71.75, respectively, which make them very interesting candidates for further development of more potent and selective anti-HCV agents.
