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Biomedical subjects

G A Galegov

Publications and source records attributed to G A Galegov.

At least 19 recordsLinked to original sources
PubMed2005

Synthesis and evaluation of anti-HSV activity of new 5-alkynyl-2'-deoxyuridines.

Eight 5-alkynyl-2'deoxyuridines containing different bulky substituents have been prepared and tested against HSV-1 in Vero cells. The compounds show positive antiviral activity. There is no obvious correlation between activity and substituent size. The nature of the linker between uracil and a substituent appears to be more important for antiviral properties: nucleosides containing arylethynyl groups show higher activity.

Animals↗
PubMed2004

[Nikavir (phosphazide)--an antiretroviral agent: anti-HIV activity, toxicology, pharmacokinetics and some perspectives of its clinical use].

Nikavir (phosphazide) is an antiretroviral agent of the class of inhibitors of type 1 HIV reverse transcriptase. It was designed in Russia and is currently used in the medical practice for the treatment of HIV infection as the monotherapy or as a component of the combined therapy. It is characterized by high anti-HIV activity, low cytotoxicity and less frequent induction of HIV-1 variants with lower susceptibility to nikavir, as compared to azidothymidine. Unlike azidothymidine, nikavir induces no blood count shifts in the patients and belongs to the group of low toxic compounds. The tolerance of nikavir by HIV-infected patients is good and its therapeutic action in HIV-1 infection is marked.

Administration, Oral↗
PubMed2003

[Decrease of HIV-1 replicative capacity after serial passage in MT-4 cells under conditions of the combined antiretroviral therapy].

The replicative activity of HIV-1/IIIB was determined in MT-4 cells under conditions of combined HIV reverse transcriptase and protease inhibitors in the presence of four different drug cocktails: (1) phosphazide, didanosine, nevirapine; (2) stavudine, didanosine, nevirapine; (3) phosphazide, didanosine, nevirapine, indinavir; (4) stavudine, didanosine, nevirapine, indinavir. The concentration of every inhibitor was 10 times higher than the 50% effective concentration. Alpha interferon was used as a natural antiretroviral agent in addition. The virus was subjected to 5 serial passages in the presence of the drug cocktails and then to 5 serial passages without the agents using cocultivation of infected and uninfected cells at ratio 1:5 to increase virus activity. Virus replication in the presence of all the drug combinations resulted in the appearance of HIV-1 variants with low replicative activity that was insignificantly increased during further passages even without the antiretroviral agents. If extrapolated to the clinical practice, these results indicate that all the drug cocktails were effective inhibitors of HIV-1 replication because the virus variants with high replicative activity did not emerge. Moreover, the results showed that the clinical use of the drug cocktails was promising.

Anti-HIV Agents↗
PubMed2002

[3-substituted analogs of remantadine: synthesis and antiherpetic activity in Vero cells].

Chemical synthesis of 3-substituted analogues of remantadine is described. Derivatives IIIb and IIIc when compared with remantadine had not only potent activity against ethalon herpes simplex type 1 virus strain but also were active against herpes virus resistant to aciclovir. Compound IIIc demonstrated virulecidal effect. Combination of IIIc + aciclovir had additive effect against ethalon herpes simplex type 1 virus strain. Investigated 3-substituted analogues demonstrated low activity in the model system of influenzae virus. No antiviral activity was demonstrated in the model system of Syndbys virus (though compounds were evaluated in subtoxic concentrations).

Acyclovir↗
PubMed2000

[Inhibition of the reproduction of strains of the herpes simplex virus type 1 with drug resistance].

Inhibition of type-1 herpes simplex strains resistant to acyclovir, phosphonoacetic acid and their combination by combined use of three drugs with different mechanisms of action capable of suppressing reproduction of the acyclovir resistant strain was studied. The combinations used were the following: Ara-A + ribavirin + phosphonoformic acid, Xylo-A + ribavirin + phosphonoformic acid and Ph-ACH + Ara-A + ribavirin. The former two combinations had a synergistic action on the standard strain L2 whose drug susceptibility had not undergone changes as well as on the acyclovir resistant strain. As for the strain resistant to phosphonoacetic acid and to acyclovir + phosphonoacetic acid the effect was additive. Ph-ACH + Ara-A + ribavirin had a marked synergistic action on all the strains tested.

Acyclovir↗
PubMed1997

[Synthesis and antiherpes activity of acyclovir phosphoesters].

9-(Hydroxyethyloxymethyl)guanine (acyclovir) phosphite and fluorophosphate were synthesized by the reactions of acyclovir with phosphorus trichloride in triethyl phosphate and with fluorophosphoric acid in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride, respectively, and characterized by the data of 1H and 31P NMR and mass spectra. These products selectively inhibit reproduction of the herpes simplex virus type 1 in the Vero cell culture, the phosphite being also substantially active against a herpes virus strain resistant to acyclovir.

Acyclovir↗
PubMed1995

[Action of para-aminobenzoic acid and its combination with acyclovir in herpetic infection].

The effect of para-amino benzoic acid (PABA) on the virus of Herpes simplex (VHS-1, strain L2) was studied and it was shown to be active in vitro and in vivo. The action of PABA was virucidal in the culture of the cell-free virus-containing material. It lowered the death rate of the laboratory mice with experimental herpetic encephalitis (intraperitoneal contamination) at the average by 40 per cent and increased the mean life-span of the animals significantly decreasing the virus titre in the mouse brain. PABA was not toxic with respect to the Vero cells thus not preventing the virus-induced cytopathic effect in the cultures. However, PABA showed high ability to potentiate the antiherpetic action of acyclovir (Zovirax, acycloguanosine) in the infected cultures when acyclovir was used in inactive concentrations.

4-Aminobenzoic Acid↗
PubMed1992

[Reverse transcriptase inhibitors and the therapy of HIV infection].

Azidothymidine (retrovir) and didesoxyinosine, which represent nucleoside agents, are major remedies in the treatment of HIV infection and acquired immunodeficiency syndrome (AIDS). The paper describes the molecular mechanism of their action. It implicates that triphosphates of these nucleosides selectively suppress the activity of reverse transcriptase (RNA-dependent DNA polymerase) of HIV by a termination mechanism. This results in effective inhibition of HIV reproduction and recovery of lymphocyte count and yields marked therapeutical benefits. The new generation anti-HIV agents are nucleoside-based phosphonates which were discovered by Russian investigators in 1987. The agents having a significant anti-HIV activity are low toxic. Emphasis is made on combined therapy of HIV infection, which holds much promise.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Effect of various adamantane compounds on the reproduction of Sindbis virus. Isolation and properties of a resistant strain].

Rimantadine and its structural analogs, i. e. amide of 1-adamantane carboxylic acid (AACA) and 1-adamantane acetic acid amide, were shown to be able to inhibit reproduction of Sindbis virus in culture Vero cells. AACA had the maximum antiviral activity. Subcultures of the initial sensitive population of Sindbis virus in the presence of AACA led to formation of mutants resistant to AACA as well as to rimantadine, adamantane acetic acid amide and ammonium chloride. The Sindbis virus population was heterogenous in sensitivity to AACA, which was evident from isolation of separate clones with various levels of sensitivity to the above mentioned compounds from the population. It was found that reproduction of the AACA sensitive and resistant strains of Sindbis virus differed: the latent period of the resistant strain was 2 hours longer than that of the sensitive strain. The same effect was observed in the comparative study on synthesis of the virus-specific RNA.

Animals↗
PubMed1991

[3'-Mercapto-3'-deoxythymidine-5'-triphosphate as a terminator of DNA synthesis catalyzed by RNA-dependent DNA-polymerases].

3'-Mercapto-3'-deoxy-TTP was synthesized and tested as DNA chain terminator nucleotide for calf thymus alpha DNA polymerase, E. coli DNA polymerase I (Klenow fragment), terminal deoxyribonucleotidyltransferase (Bollum enzyme) and reverse transcriptase from AMV- and HIV-I-viruses. It was shown that the compound terminates DNA chain elongation by reverse transcriptases selectively and irreversibly. Other tested DNA polymerases do not use this nucleotide analogue as a substrate. 3'-Mercapto-3'-deoxythymidine was tested on lymphoblastoid T-cell line MT-4 with HIV-viruses and shown to suppress viruses as efficiently as 3'-azido-3'-deoxythymidine.

Animals↗
PubMed1990

[Comparative inhibitory analysis of DNA biosynthesis catalyzed by retrovirus reverse transcriptase].

Comparative study of DNA biosynthesis inhibition, catalyzed by avian myeloblastose virus (AMV) reverse transcriptase (RT), human immunodeficiency virus (HIV) recombinant and native RT, has been performed. 3'-Azido-2',3'-dideoxythymidine 5'-triphosphate (AzTTP); 3'-azido-2',3'-dideoxythymidine 5'-methylenephosphonate-diphosphate: 3'-azido-2',3'-dideoxythymidine 5'-phosphate-phosponoacetate; 3'-azido-2',3'-dideoxythymidine 5'-phosphate-dibromomethylenephosphonate; 2',3'-O-isopropylidenecytidine 5'-methylenephosphonate-diphosphate (rC-IP-MPDP) were used as inhibitors. AzTTP proved to by the most active inhibitor (its activity against HIV RT is higher than against AMV RT), although not selective as the phosphonates; only rC-iP-MPDP has low selectivity.

Avian Myeloblastosis Virus↗