Dual inhibition of HCV and HIV by ring-expanded nucleosides containing the 5:7-fused imidazo[4,5-e][1,3]diazepine ring system. In vitro results and implications.
Examples of ring-expanded nucleosides (RENs), represented by general structures 1 and 2, exhibited dual anti-HCV and anti-HIV activities in both cell culture systems and the respective target enzyme assays, including HCV NTPase/helicase and human RNA helicase DDX3. Since HCV is a leading co-infection in late stage HIV AIDS patients, often leading to liver cirrhosis and death, the observed dual inhibition of HCV and HIV by the target nucleoside analogues has potentially beneficial implications in treating HIV patients infected with HCV.
Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Ning
N
Zhang
Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Peng
P
Zhang
Department of Molecular Biology, John Paul II Catholic University of Lublin, Lublin, Poland.
Andrea
A
Baier
INSERM U871, Molecular Physiopathology & New Treatments of Viral Hepatitis, 151 Cours A. Thomas, 69003 Lyon Cedex 03, France.
Lucyna
L
Cova
Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: hosmane@umbc.edu.
Ramachandra S
RS
Hosmane
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001381:Azepines; D007093:Imidazoles; C000592173:imidazo(4,5-e)(1,3)diazepine; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
Antiviral compounds; Dual inhibitors of HCV and HIV; Hepatitis C virus (HCV); Human immunodeficiency virus (HIV); Imidazo[4,5-e][1,3]diazepines; In vitro screening; Inhibition of HCV NTPase/helicase; Inhibition of RNA helicase DDX3; Organic synthesis; Ring-expanded nucleosides