Mechanisms of Inhibition of Various Cellular DNA and RNA Polymerases by Several Flavonoids

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Abstract
Four flavonoids (i.e., baicalein, quercetin, quercetagetin, and myricetin), known to be inhibitors of HIV-reverse transcriptase, have been shown to be more or less inhibitory to the activities of various cellular DNA and RNA polymerases. The degree of the inhibition varied depending on the combination of the flavonoid and the enzyme species: baicalein was moderately inhibitory to DNA polymerase β and E. coli DNA polymerase I; quercetin was strongly inhibitory to DNA polymerase β and E. coli RNA polymerase and moderately inhibitory to DNA polymerase I; quercetagetin was a potent inhibitor for all of DNA polymerases α, β, γ, and I and RNA polymerase; myricetin was a strong inhibitor of DNA polymerases α and I and RNA polymerase. However, terminal deoxynucleotidyltransferase was virtually insensitive to inhibition by these flavonoids. The inhibition by the flavonoids was due to competition with the template-primer in the case of the DNA polymerases, whereas the inhibition was due to competition with the triphosphate substrate (GTP) in the case of RNA polymerase. The K1 values of these flavonoid inhibitors for DNA and RNA polymerases was determined.

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