Inhibitory effects of quinones on RNase H activity associated with HIV-1 reverse transcriptase

In an effort to develop new drugs preventing the growth of human immunodeficiency virus (HIV), we developed an in vitro assay method of ribonuclease H (RNase H) activity associated with reverse transcriptase (RT) from HIV‐1. Some naphthoquinones, such as 1,4‐naphthoquinone (1), vitamin K3 (2), juglone (3) and plumbagin (6), moderately inhibited RNase H activity, and others, including naphthazarin (5) and shikonins (8–9, 18–23), showed weak inhibition. Diterpenoid quinones, tanshinones (24–28), had also moderate inhibition against RNase H activity. Of these quinones, compound 1 showed the most potent inhibition on RNase H activity with a 50% inhibitory concentration (IC50) of 9.5 μM, together with moderate inhibition against RNA‐dependent and DNA‐dependent DNA polymerase (RDDP and DDDP) activities with IC50 values of 69 and 36 μM, respectively. Compounds 3 and 5 showed significant inhibition against RDDP (IC50 = 8 and 10 μM, respectively) and DDDP (IC50 = 5 and 7 μM, respectively) activities. The structure‐activity relationship of the naphthoquinones suggested that non‐hydroxylated naphthoquinones (1 and 2) showed significant inhibition of RNase H activity, whereas 5‐hydroxylated naphthoquinones (3 and 5) showed potent inhibition against RDDP and DDDP activities. Copyright ­© 2002 John Wiley & Sons, Ltd.