Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava

Abstract

The bioassay-directed isolation of a marine brown alga, Ecklonia cava, afforded four phlorotannin derivatives, eckol (1), 8,8′-bieckol (2), 8,4?-dieckol (3), and phlorofucofuroeckol A (4). Among these compounds, 2 and 3 exhibited an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease. Specifically, they inhibited the RT more potently than the protease. The inhibitory activity of compound 2 (IC50, 0.51 μM) against HIV-1 RT was comparable to that of nevirapine (IC50, 0.28 μM), a reference compound. An enzyme kinetic assay showed that this compound inhibited the RNA-dependent DNA synthesis activity of HIV-1 RT noncompetitively against dUTP/dTTP with a K i value of 0.78 μM. With respect to the homopolymeric template/primer, (rA)n(dT)15, 8,8′-bieckol (2) displayed an uncompetitive type of inhibition (Ki, 0.23 μM). ? 2004 Pharmaceutical Society of Japan.