title: Design, synthesis, assessment, and molecular docking of novel pyrrolopyrimidine (7-deazapurine) derivatives as non-nucleoside hepatitis C virus NS5B polymerase inhibitors.
abstract: Hepatitis C virus (HCV) infection is highly persistent and presents an unmet medical need requiring more effective treatment options. This has spurred intensive efforts to discover novel anti-HCV agents. The RNA-dependent RNA polymerase (RdRp), NS5B of HCV, constitutes a selective target for drug discovery due to its absence in human cells; also, it is the centerpiece for viral replication. Here, we synthesized novel pyrrole, pyrrolo[2,3-d]pyrimidine and pyrrolo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine derivatives. The non-toxic doses of these compounds on Huh 7.5 cell line were determined and their antiviral activity against HCVcc genotype 4a was examined. Compounds 7j, 7f, 5c, 12i and 12f showed significant anti HCV activity. The percent of reduction for the non-toxic doses of 7j, 7f, 5c, 12i and 12f were 90%, 76.7±5.8%, 73.3±5.8%, 70% and 63.3±5.8%, respectively. The activity of these compounds was interpreted by molecular docking against HCV NS5B polymerase enzyme.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
authors.forename: Mosaad S
authors.initials: MS
authors.lastname: Mohamed
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
authors.forename: Amira I
authors.initials: AI
authors.lastname: Sayed
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khedr
authors.affiliation: Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Ain Helwan, University Campus, 11795 Cairo, Egypt; Center for Scientific Excellence 'Helwan Structural Biology Research (HSBR)', Cairo, Egypt. Electronic address: sameh_soror@pharm.helwan.edu.eg.
authors.forename: Sameh H
authors.initials: SH
authors.lastname: Soror
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; D017361:Viral Nonstructural Proteins; C512929:7-deazapurine; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Antiviral drugs; HCV; Molecular modeling; NS5B polymerase; Pyrrolopyrimidine