Giuseppe
Emeritus
A NOVEL AZOLO-1,2,4-TRIAZINE-DERIVED INHIBITOR OF INFLUENZA A AND B VIRUS REPLICATION: ANTIVIRAL PROPERTIES, METABOLISM, AND PHARMACOKINETICS. (Antimicrob Agents Chemother., abstract, edited)
31. Antimicrob Agents Chemother. 2010 Mar 1. [Epub ahead of print]
A NOVEL AZOLO-1,2,4-TRIAZINE-DERIVED INHIBITOR OF INFLUENZA A AND B VIRUS REPLICATION: ANTIVIRAL PROPERTIES, METABOLISM, AND PHARMACOKINETICS.
Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E, Yanvarev D, Ivanov A, Smirnova O, Kochetkov S, Chupakhin O, Kukhanova M. - Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Postovsky Institute of Organic Synthesis, Ural Division of Russian Academy of Sciences, Ekaterinburg, Russia; Research Institute of Influenza, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated a novel effective inhibitor of human influenza A and B virus triazavirine (2-methylthio-6-nitro-1,2,4-triazolo[5,1-C]-1,2,4-triazine-7(4H)-one, TZV). TZV suppressed replication of influenza virus in cell culture, chicken chorioallantoic membranes, protected mice from death caused by type A and B influenza viruses. TZV was also effective against rimantadine-resistant influenza strain and avian influenza A virus strain H5N1. Pharmacokinetic parameters and bioavailability of TZV were calculated after TZV administration in rabbits. The TZV metabolite (2-methylthio-6-amino-1,2,4-triazolo[5,1-s]-1,2,4-triazin(e)-7(4H)-one, AMTZV) was discovered in cell cultures HEK 293T and Huh7, liver homogenate, and in rabbit blood after TZV intragastric administration. The AMTZV was non-toxic and inactive as influenza inhibitor in cell culture. Most likely metabolite is a product of TZV elimination.
PMID: 20194696 [PubMed - as supplied by publisher]
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31. Antimicrob Agents Chemother. 2010 Mar 1. [Epub ahead of print]
A NOVEL AZOLO-1,2,4-TRIAZINE-DERIVED INHIBITOR OF INFLUENZA A AND B VIRUS REPLICATION: ANTIVIRAL PROPERTIES, METABOLISM, AND PHARMACOKINETICS.
Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E, Yanvarev D, Ivanov A, Smirnova O, Kochetkov S, Chupakhin O, Kukhanova M. - Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia; Postovsky Institute of Organic Synthesis, Ural Division of Russian Academy of Sciences, Ekaterinburg, Russia; Research Institute of Influenza, Russian Academy of Medical Sciences, St. Petersburg, Russia.
Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated a novel effective inhibitor of human influenza A and B virus triazavirine (2-methylthio-6-nitro-1,2,4-triazolo[5,1-C]-1,2,4-triazine-7(4H)-one, TZV). TZV suppressed replication of influenza virus in cell culture, chicken chorioallantoic membranes, protected mice from death caused by type A and B influenza viruses. TZV was also effective against rimantadine-resistant influenza strain and avian influenza A virus strain H5N1. Pharmacokinetic parameters and bioavailability of TZV were calculated after TZV administration in rabbits. The TZV metabolite (2-methylthio-6-amino-1,2,4-triazolo[5,1-s]-1,2,4-triazin(e)-7(4H)-one, AMTZV) was discovered in cell cultures HEK 293T and Huh7, liver homogenate, and in rabbit blood after TZV intragastric administration. The AMTZV was non-toxic and inactive as influenza inhibitor in cell culture. Most likely metabolite is a product of TZV elimination.
PMID: 20194696 [PubMed - as supplied by publisher]
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