Inhibition of HIV-reverse transcriptase activity by asterriquinone and its analogues.

Abstract Asterriquinone (ARQ; 2,5-bis-[1′-(1″,1″-dimethyl-2″-propenyl)-indol-3′-yl]-3,6-dihydroxy-1,4-benzoquinone) and its three analogues [ e.e. , 3,6-dihydroxy-2-[2′-(1″,1″-dimethyl-2″-propenyl)-indol-3′-yl]-5-[1′,7′-(1″,1″-dimethylpropano)-indol-3′-yl]-1,4-benzoquinone (B1-4), 3,6-dihydroxy-2-[2′-(1″,1″-dimethyl-2″-propenyl)-indol-3′-yl]-5-indol-3′-yl-1,4-benzoquinone (C1-1) and 3,6-dihydroxy-2,5-diindol-3′-yl-1,4-benzoquinone (D-1)] were found to be strong inhibitors of the activity of reverse transcriptase from human immunodeficiency virus type-1. Under the reaction conditions employed, the enzyme activity was inhibited by more than 70% in the presence of 10 μM each of these compounds. The mode of inhibition by these compounds was competitive with respect to the template·primer, (rA) n ·(dT) 12–18 , and noncompetitive with respect to the triphosphate substrate, dTTP. The Ki values of HIV-1 reverse transcriptase were determined to be 2.3, 1.5, 0.1 and 0.3 μM for ARQ, B1-4, C1-1 and D-1, respectively.