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 K 3 ( 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 (IC 50 ) of 9.5 μ M , together with moderate inhibition against RNA‐dependent and DNA‐dependent DNA polymerase (RDDP and DDDP) activities with IC 50 values of 69 and 36 μ M , respectively. Compounds 3 and 5 showed significant inhibition against RDDP (IC 50  = 8 and 10 μ M , respectively) and DDDP (IC 50  = 5 and 7 μ M , 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.