title: Inhibition of avian myeloblastosis virus reverse transcriptase and virus inactivation by metal complexes of isonicotinic acid hydrazide.
abstract: The cupric and ferric complexes of isonicotinic acid hydrazide (INH) inhibit the DNA synthesis catalysed by avian myeloblastosis virus (AMV) reverse transcriptase. The inhibition was to the extent of 95% by 50 microM of cupric-INH complex and 55% by 100 microM of ferric-INH complex. These complexes have been found to bind preferentially to the enzyme than to the template-primer. Kinetic analysis showed that the cupric-INH complex is a non-competitive inhibitor with respect to dTTP. The time course of inhibition has revealed that the complexes are inhibitory even after the initiation of polynucleotide synthesis. In vivo toxicity studies in 1-day-old chicks have shown that the complexes are not toxic up to a concentration of 500 microgram per chick. Infection of the 1-day-old chicks with AMV pretreated with 150 microgram of either of the complexes prevented symptoms of leukemia due to virus inactivation.
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000517:prevention & control; D001354:Avian Leukosis Virus / Q000187:drug effects*; D009189:Avian Myeloblastosis Virus / Q000187:drug effects* / Q000201:enzymology; D001667:Binding, Competitive; D002645:Chickens; D003300:Copper / Q000494:pharmacology* / Q000633:toxicity; D004279:DNA, Viral / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology* / Q000633:toxicity; D007501:Iron / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology* / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D004279:DNA, Viral; D005290:Ferric Compounds; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D003300:Copper; D007501:Iron; D007538:Isoniazid