The inhibition of human immunodeficiency virus type 1 reverse transcriptase by avarol and avarone derivatives.
We have analyzed the effects of several natural compounds related to avarols and avarones on the catalytic functions of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The most potent substances, designated as avarone A,B and E and avarol F, inhibited indiscriminately the enzymatic activities of HIV-1 RT, namely the RNA-dependent and DNA-dependent DNA polymerase as well as the ribonuclease H. The inhibition of the DNA polymerase activity was found to be non-competitive with respect to either the template-primer or the deoxynucleotidetriphosphate. These studies suggest that the hydroxyl group at the ortho position to the carbonyl group at the quinone ring is involved in blocking the RT activity. The identification of the active site of the inhibitors will hopefully lead to the rational design of new potent anti-HIV drugs.
Department of Cell Biology and Histology, Sackler School of Medicine, Tel-Aviv University, Israel.
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D000818:Animals; D053138:Cyclohexenes; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology; D004722:Endoribonucleases / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000201:enzymology*; D007700:Kinetics; D011161:Porifera / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors; D016914:Ribonuclease H; D012717:Sesquiterpenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D053138:Cyclohexenes; D003848:Deoxyguanine Nucleotides; D018894:Reverse Transcriptase Inhibitors; D012717:Sesquiterpenes; C046374:avarone; C029603:deoxyguanosine triphosphate; D004722:Endoribonucleases; D016914:Ribonuclease H; C023663:avarol