Inhibition of reverse transcriptase activity by benzophenanthridine alkaloids.
Benzophenanthridine alkaloids, fagaronine 4, O-methylfagaronine 5, nitidine 1, allonitidine 3 and methoxydihydronitidine 2 have been shown to posses inhibitory activity against reverse transcriptase of RNA tumor viruses. The enzyme inhibition (50%) by these alkaloids was found in the range of 6-60 microgram per milliliter of the reaction mixture when polynucleotide-oligodeoxynucleotide complexes were used as template primers. The results suggested that the benzophenanthridine alkaloids interacted with the template primers (particularly of the A:T base pairs) and not with the enzyme proteins. Kinetics reaction of the reverse transciptase inhibition showed that the alkaloids stopped the DNA polymerase synthesis instantly, probably by interacting with the template primer.
D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D007700:Kinetics; D010617:Phenanthridines / Q000378:metabolism / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011925:Rauscher Virus / Q000201:enzymology; D018894:Reverse Transcriptase Inhibitors; D013698:Templates, Genetic
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D010617:Phenanthridines; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase