Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6.
Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of α-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia. Electronic address: kozlovmv@hotmail.com.
Maxim V
MV
Kozlov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Alla A
AA
Kleymenova
Chumakov Institute of Poliomyelitis, Russian Academy of Medical Sciences, 142782 Moscow Region, Russia.
Lyudmila I
LI
Romanova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Konstantin A
KA
Konduktorov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Kamila A
KA
Kamarova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Olga A
OA
Smirnova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Vladimir S
VS
Prassolov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
Sergey N
SN
Kochetkov
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D017955:Poliovirus / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects; D014780:Viruses
D000998:Antiviral Agents; D006877:Hydroxamic Acids; D011725:Pyridines; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
Benzohydroxamic acids; Hepatitis C virus; Histone deacetylase 6; Pyridine hydroxamic acids; α-Tubulin