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Inhibition of reverse transcriptase activity by benzophenanthridine alkaloids

M L Sethi

    Lloydia
    |March 1, 1979
    PubMed
    Summary
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    Benzophenanthridine alkaloids inhibit RNA tumor virus reverse transcriptase by interacting with template primers, not the enzyme itself. This interaction halts DNA synthesis, suggesting a novel antiviral mechanism.

    Area of Science:

    • Biochemistry
    • Virology
    • Medicinal Chemistry

    Background:

    • Reverse transcriptase is a key enzyme in RNA tumor viruses.
    • Benzophenanthridine alkaloids are a class of natural compounds with potential biological activities.

    Purpose of the Study:

    • To investigate the inhibitory activity of benzophenanthridine alkaloids against RNA tumor virus reverse transcriptase.
    • To elucidate the mechanism of enzyme inhibition.

    Main Methods:

    • Enzyme inhibition assays using polynucleotide-oligodeoxynucleotide complexes as template primers.
    • Kinetic analysis of enzyme inhibition.

    Main Results:

    • Several benzophenanthridine alkaloids (fagaronine, O-methylfagaronine, nitidine, allonitidine, methoxydihydronitidine) demonstrated inhibitory activity.

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  • Inhibition occurred at concentrations of 6-60 µg/mL.
  • Alkaloids primarily interacted with template primers, especially A:T base pairs, rather than enzyme proteins.
  • Inhibition was rapid, instantly stopping DNA polymerase synthesis.

    • Conclusions:

    • Benzophenanthridine alkaloids exhibit potent inhibitory effects on reverse transcriptase.
    • The mechanism involves interaction with template primers, suggesting a non-competitive inhibition.
    • These findings highlight the potential of benzophenanthridine alkaloids as antiviral agents targeting reverse transcriptase.