Inhibition of HIV-1 reverse transcriptase and protease by phlorotannins from the brown alga Ecklonia cava.
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 (IC(50), 0.51 microM) against HIV-1 RT was comparable to that of nevirapine (IC(50), 0.28 microM), 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 microM. With respect to the homopolymeric template/primer, (rA)n(dT)15, 8,8'-bieckol (2) displayed an uncompetitive type of inhibition (K(i), 0.23 microM).
Ahn
Mi-Jeong
MJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-752, Korea.
Yoon
Kee-Dong
KD
Min
So-Young
SY
Lee
Ji Suk
JS
Kim
Jeong Ha
JH
Kim
Tae Gyun
TG
Kim
Seung Hee
SH
Kim
Nam-Gil
NG
Huh
Hoon
H
Kim
Jinwoong
J
D016333:HIV Protease / Q000737:chemistry*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000459:Phaeophyceae / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*; D012194:RNA-Directed DNA Polymerase / Q000302:isolation & purification; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013634:Tannins / Q000737:chemistry* / Q000302:isolation & purification
D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013634:Tannins; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease