Novel symmetrical phenylenediamines as potential anti-hepatitis C virus agents.
BACKGROUND
Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection.


METHODS
With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay.


RESULTS
Among the newly designed compounds, one new structural family was found to inhibit the hepatitis C virus-1b replication in the micromolar range. This scaffold was chosen for further exploration and different novel analogues were synthesised and evaluated.


CONCLUSIONS
Different new inhibitors of the hepatitis C virus genotype 1b replication were identified. Some of the new compounds show mild inhibition of the NS3 helicase enzyme.
1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, UK.
Marcella
M
Bassetto
1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, UK.
Salvatore
S
Ferla
2 Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Pieter
P
Leyssen
2 Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Johan
J
Neyts
3 Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, USA.
Mark M
MM
Yerukhimovich
3 Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, USA.
David N
DN
Frick
1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, UK.
Rachel
R
O'Donnell
1 Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff, UK.
Andrea
A
Brancale
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010655:Phenylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D010655:Phenylenediamines
Hepatitis C virus; inhibitors