DIFFERENTIAL INHIBITORY EFFECTS OF SOME CATECHIN DERIVATIVES ON THE ACTIVITIES OF HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE AND CELLULAR DEOXYRIBONUCLEIC AND RIBONUCLEIC-ACID POLYMERASES

The two components of Camellia sinensis (tea plant) [i.e., (−)-epicatechin gallate and (−)-epigallocatechin gallate] were found to differentially inhibit the activities of reverse transcriptase and cellular DNA and RNA polymerases. Under the assay conditions optimized for each enzyme species, the strongest inhibition by these compounds was observed with reverse transcriptase. The concentrations of (−)-epicatechin gallate and (−)-epigallocatechin gallate required for 50% inhibition of the activity of human immunodeficiency virus (HIV) reverse transcriptase were in the range of 0.01–0.02 μg /mL. On the other hand, neither (−)-epicatechin, (−)-epigallocatechin, nor gallic acid, the constituents of (−)-epicatechin gallate and (−)-epigallocatechin gallate, was inhibitory to the activity of HIV reverse transcriptase at concentrations up to 1 μg /mL. The mode of inhibition of reverse transcriptase and other DNA polymerases by these compounds was competitive with respect to the template-primer, whereas the mode of inhibition of RNA polymerase was competitive with respect to the nucleotide substrate. The Ki values of HIV reverse transcriptase for (−)-epicatechin gallate and (−)-epigallocatechin gallate were determined to be 7.2 and 2.8 nM, respectively, which are smaller by 1–2 orders of magnitude than the Ki's of other DNA and RNA polymerases for these compounds. © 1990, American Chemical Society. All rights reserved.