Inhibition of Reverse Transcriptase Activity by Benzophenanthridine Alkaloids

Abstract

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.

Antibacterial and antifungal activities of different parts of Tribulus terrestris L. growing in Iraq

“…Alkaloids may be useful against HIV infection (Sethi, 1979) as well as intestinal infections associated with AIDS (McDevitt et al, 1996). Berberine and harmane are important representatives of the alkaloid group.…”

Enzyme Inhibition VI: Inhibition of Reverse Transcriptase Activity by Protoberberine Alkaloids and Structure–Activity Relationships

“…The 70s RNA4 from MuLV was purified by a published method (33). Reverse transcriptase assay and enzyme inhibition were carried out by a method previously reported (21). Appropriate concentrations of the protoberberine alkaloids5.6 were dissolved in dimethyl sulfoxide.…”

“…In view of the observation that some benzophenanthridine alkaloids are potential inhibitors of reverse transcriptase activity (20)(21)(22), the structurally related protoberberine alkaloids were examined for their effect on reverse transcriptase activity of RNA tumor viruses. It was considered worthwhile to screen these alkaloids for their antireverse transcriptase activity and correlate this activity with their structures and their antileukemic activity.…”

Fagaronine, a novel antileukaemic alkaloid

“…It would seem that FGN acts by intercalation into initiation complexes within the DNA double-strand or into double-stranded regions of RNA (Comoe et al, 1988;Pezzuto et al, 1983;Sethi and Sethi, 1975;Sethi, 1979;Torres and Baez, 1986). Specificity with respect to the bases adenine and thymine, though occasionally acknowledged, was rejected by Pezzuto et al (1983).…”

“…50% inhibition was obtained with 26 nmoles FGN or 109 nmoles NTD (Sethi and Sethi, 1975;Sethi, 1979).…”