brivudine and ibacitabine

We tested the in vitro sensitivity of Macropodid Herpesvirus 2 to eight commonly used anti-herpetic compounds using plaque reduction tests, March and April, 1995. The virus was most susceptible to inhibition by (E)-5-(2'-bromovinyl)-2'-deoxyuridine and adenine 9-beta-D-arabino-furanoside. Both compounds have been used for anti-herpetic therapy in humans and may prove useful in the treatment of macropodoids in captivity.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinonucleosides; Bromodeoxycytidine; Bromodeoxyuridine; Cell Line; Cytarabine; Deoxycytidine; Herpesviridae; Herpesviridae Infections; Idoxuridine; Macropodidae; Microbial Sensitivity Tests; Neutralization Tests; Thymidine; Trifluridine; Vidarabine

In experiments using yeast, without addition of an external metabolic activation system, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was co-mutagenic and showed an insignificant anti-recombinogenic effect in combination with triethylene melamine (TEM). In the presence of activating S9-mix, the anti-recombinogenicity and co-mutagenicity could clearly be seen. At higher concentrations the co-mutagenic effect was converted into anti-mutagenicity. The other three 5-substituted pyrimidine nucleoside analogs were tested only in the presence of activating S9-mix and showed similar effects. As TEM is a direct alkylating agent that is inactivated by liver microsomes, the higher activity in presence of S9-mix can be interpreted as resulting from metabolic activation of the 5-substituted pyrimidine nucleoside analogs. In previous experiments using yeast bacteria, Drosophila or mice, tumor promoters were co-recombinogenic/anti-mutagenic, and co-carcinogens were co-mutagenic/anti-recombinogenic. Thus, there is not only an operational difference between tumor promoters and co-carcinogens but a real difference in respect to their genetic effectiveness. As up to now only co-carcinogens have shown co-mutagenic and anti-recombinogenic effects, it is perhaps possible that, within a certain concentration range, 5-substituted pyrimidine nucleoside analogs may have co-carcinogenic activity in carcinogenicity tests. At higher concentrations the co-carcinogenic effect may be converted into an anti-carcinogenic one.

Topics: Animals; Bromodeoxycytidine; Bromodeoxyuridine; Deoxycytidine; Dose-Response Relationship, Drug; Genes, Fungal; Heterozygote; Idoxuridine; Liver; Male; Mutagens; Mutation; Rats; Recombination, Genetic; Saccharomyces cerevisiae; Triethylenemelamine; Trifluridine