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I. D. Konstantinova I. V. Fateev G. A. Galegov P. G. Deryabin A. G. Botikov I. S. Muzyka D. K. L’vov A. I. Miroshnikov 《Russian Journal of Bioorganic Chemistry》2013,39(5):530-538
The biotechnological method of synthesis of the antiviral drug ribavirin based on the transglycosylation reaction was improved due to the addition of catalytic amounts of sodium arsenate. This approach allows us to hydrolyze the excess natural nucleoside guanosine, a ribose donor, and, hence, made the composition of the reaction mixture less complicated, thus facilitating the process of ribavirin isolation. It was shown that in cell cultures the combination of ribavirin and oseltamivir carboxylate inhibited the replication of the influenza A virus more effectively than each of them alone. Similar results were obtained in experiments on laboratory animals (mouse Balb/c) infected with the influenza A virus H3N2/Aichi/68 strain. 相似文献
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Aleksandrova L. A. Andronova V. L. Karpenko I. L. Skoblov Yu. S. Adani A. Galegov G. A. 《Russian Journal of Bioorganic Chemistry》2002,28(5):412-418
A number of new 5"-phosphonate derivatives of 4"-thio-5-ethyl-2"-deoxyuridine (TEDU) were synthesized. These compounds displayed a low cytotoxicity and, except for TEDU 5"-fluorophosphate, antiherpes activity similar to that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (pencyclovir). 5"-Ethoxycarbonylphosphonate and 5"-aminocarbonylphosphonate of TEDU were also found to suppress the reproduction of herpes simplex type 1 virus, which is resistant to acyclovir. 相似文献
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Karpenko IL Jasko MV Andronova VL Ivanov AV Kukhanova MK Galegov GA Skoblov YS 《Nucleosides, nucleotides & nucleic acids》2003,22(3):319-328
Phosphonate derivatives of acyclovir containing phosphorous acid and ethoxycarbonylphosphonic acid residues as well as their isopropyl esters were prepared. They selectively inhibited the herpes simplex virus 1 reproduction in Vero cell culture, the efficacy of esters being 3-4 times higher than that of ACV. The hydrolysis of the synthesized compounds was studied in the PBS buffer and human blood serum. 相似文献
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V. N. Stepanenko R. S. Esipov A. I. Miroshnikov V. L. Andronova G. A. Galegov M. V. Yasko A. A. Gus’kova A. Yu. Skoblov Yu. S. Skoblov 《Russian Journal of Bioorganic Chemistry》2011,37(4):436-440
Thymidine kinase UL23 gene (EC 2.7.1.145) from the L2 acyclovir-sensitive strain of herpes simplex virus type 1 was cloned and expressed in E. coli. The enzyme was purified by chromatography to the purity of 90% according to PAG electrophoresis data. The Michaelis constants
for the reactions with thymidine and acyclovir were determined. The enzyme was found to phosphorylate modified nucleosides,
particularly 3′-deoxythymidine, 3′-deoxy-2′,3′-didehydrothymidine, 2′,3′-dideoxycytidine, 9-[(hydroxyethyl)methyl]guanine,
E-5-(2-bromovinyl-2′-deoxyuridine, 9-(1,3-dihydroxy-2-propoxymethyl)guanine, 2′,3′-dideoxydehydrothymidine, β-L-2′,3′-dideoxy-3′-thiacytidine, and 3′-fluoro-3′-deoxythymidine. Some properties of the purified enzyme were compared with
those of thymidine kinases of other herpes simplex virus strains. It was shown that acyclovir H-phosphonate inhibited the
enzyme. 相似文献
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Natalia F. Zakirova Alexander V. Shipitsyn Maxim V. Jasko Maria M. Prokofjeva Valeria L. Andronova Georgiy A. Galegov Vladimir S. Prassolov Sergey N. Kochetkov 《Bioorganic & medicinal chemistry》2012,20(19):5802-5809
The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity. 相似文献
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