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D Derse

Publications and source records attributed to D Derse.

57 records · Page 4Linked to original sources
PubMed1981

Mode of action of phosphonoformate as an anti-herpes simplex virus agent.

Phosphonoformate inhibited the replication of Herpes simplex virus (HSV) type 1 and type 2 in culture. The concentration required to inhibit the replication of both types of virus by 2 logs at 28 h post-infection was approximately 150 microM. It was more potent than phosphonoacetate against the growth of both virus types. A virus mutant which is resistant to phosphonoacetate was cross-resistant to phosphonoformate. Arsonoacetate, at 300 microM, had no antivirus activity. Phosphonoformate also inhibited HeLa and KB cell growth; at a concentration of about 500 microM, cell growth was inhibited by 50%. The anti-cell growth effects of the drug were completely reversible. The antivirus effect of phosphonoformate was partially reversible, depending on the time and duration of exposure of infected cultures to the drug. To obtain the maximum antivirus effect, phosphonoformate had to be added within the first 3 h post-virus-infection and be continuously present for at least 18 h. Phosphonoformate, added at 0 h post-infection, suppressed the induction of virus-specific DNA polymerase and DNAase activities. dTMP incorporation into DNA was preferentially inhibited in nuclei isolated from infected cells compared to uninfected cells, and the degree of inhibition varied with the ionic strength of the assay. Phosphonoformate was a potent inhibitor of the purified HSV-1 and HSV-2 DNA polymerases, inhibiting DNA polymerase activity by 50% at a concentration of 3 microM and ionic strength of 0.2.

Antiviral Agents↗
PubMed1981

Biological and biochemical effects of 2'-azido-2'-deoxyarabinofuranosylcytosine on human tumor cells in vitro.

2-azido-2'-deoxyarabinofuranosylcytosine (Cytarazid), recently synthesized, was found to inhibit the in vitro growth of several human cell lines by 50% at concentrations ranging from 0.06 to 0.2 microM and to prevent the replication of herpes simplex virus types 1 and 2 by 98% at 50 microM. As determined with HeLa cells, the inhibition of cell growth was partially prevented by 2'-deoxycytidine (dCyd) and cytidine but not by uridine or thymidine. Cytarazid proved resistant to deamination by human cytidine/dCyd deaminases purified from acute myelocytic leukemia blast cells and from liver, a property reflected in the inability of tetrahydrouridine to enhance the cytotoxicity of the compound. Cytarazid served as a substrate for cytoplasmic dCyd kinase partially purified from human peripheral chronic lymphocytic leukemia blast cells. At a concentration of 0.4 mM, the nucleoside analog was phosphorylated 2.6 times more effectively by this enzyme than was dCyd, the Km for Cytarazid being 250 microM. In intact HeLa cells, the triphosphate derivative of Cytarazid was the major drug metabolite formed. In these cells, the analog interfered with the incorporation of radiolabeled thymidine into DNA at a concentration and a time interval at which the incorporation of uridine into RNA and amino acids into protein was not inhibited, suggesting that interference with DNA synthesis is a primary drug effect. Further analysis showed that Cytarazid triphosphate interferes with DNA synthesis in intact HeLa cell nuclei and that it inhibits both the alpha- and beta-DNA polymerases purified from HeLa cells in a manner competitive with deoxycytidine triphosphate, with Ki's of 0.6 and 0.7 microM, respectively. Cytarazid triphosphate was not able to replace deoxycytidine triphosphate for the synthesis of DNA in either intact nuclei or in cell-free preparations; but, in the cell-free assay system, the compound was found to interfere with primer-template activity.

Biotransformation↗