Cell Metabolism of Acyclovir Phosphonate Derivatives and Antiherpesvirus Activity of their Combinations with α2‐Interferon

The combinational use of acyclovir (ACV) phosphonate esters and α2‐interferon was shown to produce a synergistic effect on inhibition of HSV‐1 replication in Vero cell cultures. Unlike other acyclovir phosphonate derivatives studied earlier, ACV H‐phosphonate is not an ACV prodrug. On penetrating into the cells, it may be directly converted into ACV monophosphate escaping dephosphonylation–phosphorylation steps.

[1]  M. Kukhanova,et al.  The Synthesis and Antiherpetic Activity of Acyclovir Phosphonate Esters , 2004, Russian Journal of Bioorganic Chemistry.

[2]  M. Skoblov,et al.  Molecular genetic analysis of thymidine kinase of the herpes simplex virus type 1 , 2005, Molecular Biology.

[3]  M. Kukhanova,et al.  Intracellular metabolism and pharmacokinetics of 5'-hydrogenphosphonate of 3'-azido-2',3'-dideoxythymidine, a prodrug of 3'-azido-2',3'-dideoxythymidine. , 2004, Antiviral research.

[4]  V. Mitkevich,et al.  Uncharged AZT and D4T derivatives of phosphonoformic and phosphonoacetic acids as anti-HIV pronucleosides. , 2004, Journal of medicinal chemistry.

[5]  M. Kukhanova,et al.  Synthesis and Antiherpetic Activity of Acyclovir Phosphonates. , 2003 .

[6]  M. Kukhanova,et al.  Synthesis and Antiherpetic Activity of Acyclovir Phosphonates , 2003, Nucleosides, nucleotides & nucleic acids.

[7]  E. De Clercq,et al.  Recent developments in herpesvirus therapy. , 2001, Herpes : the journal of the IHMF.

[8]  A. Krayevsky,et al.  P-(Alkyl)-Nucleoside 5′-Hydrogenphosphonates as Depot Forms of Antiviral Nucleotide Analogues , 2000, Nucleosides, nucleotides & nucleic acids.

[9]  A. Aubertin,et al.  Synthesis and anti-HIV activity of some novel arylphosphate and H-phosphonate derivatives of 3'-azido-2',3'-dideoxythymidine and 2',3'-didehydro-2',3'-dideoxythymidine. , 1999, Antiviral research.

[10]  G. A. Galegov,et al.  [Synthesis and antiherpes activity of acyclovir phosphoesters]. , 1997, Bioorganicheskaia khimiia.

[11]  N. Myasoedov,et al.  The synthesis of some tritium‐labelled terminators of DNA synthesis , 1994 .

[12]  P. de Miranda,et al.  Metabolic disposition of the acyclovir prodrug valaciclovir in the rat. , 1994, Drug metabolism and disposition: the biological fate of chemicals.

[13]  W. O'brien,et al.  Nucleoside metabolism in herpes simplex virus-infected cells following treatment with interferon and acyclovir, a possible mechanism of synergistic antiviral activity , 1990, Antimicrobial Agents and Chemotherapy.

[14]  P. Keller,et al.  Cytoplasmic 5'-nucleotidase catalyzes acyclovir phosphorylation. , 1985, The Journal of biological chemistry.

[15]  O. P. van Bijsterveld,et al.  Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis. , 1985, Antiviral research.

[16]  T A Krenitsky,et al.  Effects of acyclovir and its metabolites on purine nucleoside phosphorylase. , 1984, The Journal of biological chemistry.

[17]  G. Elion,et al.  Effects of acyclovir and its metabolites on hypoxanthine-guanine phosphoribosyltransferase. , 1983, Biochemical pharmacology.

[18]  H. Schaeffer,et al.  Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. , 1981, Biochemical pharmacology.

[19]  J. Connor,et al.  Disposition of intravenous radioactive acyclovir , 1981, Clinical pharmacology and therapeutics.

[20]  P. de Miranda,et al.  Metabolism of acyclovir in virus-infected and uninfected cells , 1981, Antimicrobial Agents and Chemotherapy.

[21]  R. T. Walker,et al.  Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. , 1980, The Journal of infectious diseases.

[22]  M. Berenbaum,et al.  A method for testing for synergy with any number of agents. , 1978, The Journal of infectious diseases.

[23]  H. Schaeffer,et al.  Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. , 1977, Proceedings of the National Academy of Sciences of the United States of America.