Novel 6-Aminoquinazolinone Derivatives as Potential Cross GT1-4 HCV NS5B Inhibitors

Abstract

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.

New Acetamide Derivatives of the COX-II Inhibitors-A Brief Review

“…According to a brief review of the literature on the biological activities of acetamide derivatives, they have potent antimicrobial [10], anti-inflammatory [11], anti-tumor [12], anti-HIV [13], antiviral [14], anticonvulsant [15], analgesic [16], anti-cancer [17], anti-allergic [18], sedative-hypnotic [19], and antihypertensive [20]. The synthetic adaptability of quinazolinones, which enables the synthesis of a large number of structurally different derivatives, has further aided this wide range of biological functions [21]. The chemical structures of this group of COX-II inhibitors are significantly different from those of the classical NSAIDs, mainly due to the absence of the typical amide group.…”

Importance and Application of Computational Studies in Finding New Active Quinazoline Derivatives

“…• "Computational investigation of quinazoline derivatives as potential inhibitors of hepatitis C virus NS5B polymerase" by Nain et al [59]. This study used molecular docking and molecular dynamics simulations to investigate the binding of quinazoline derivatives to the NS5B polymerase of the hepatitis C virus, with the aim of identifying potential inhibitors of viral replication [59].…”