Inhibition of human immunodeficiency virus type 1 reverse transcriptase and ribonuclease H activities by constituents of Juglans mandshurica.

From the stem-bark of Juglans mandshurica, two new naphthalenyl glucopyranosides, 1,4,8-trihydroxynaphthalene 1-O-[alpha-L-arabinofuranosyl-(1-->6)-beta-D-glucopyranoside] (1) and 1,4,8-trihydroxynaphthalene 1-O-beta-D-[6'-O-(3",5"-dihydroxy-4"-methoxybenzoyl)]glucopyranosi de (4), and two new alpha-tetralonyl glucopyranosides, 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(3",5"-dihydroxy-4"-methoxybenzoyl)]glucopyranosi de (7) and 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(3",4",5"-trihydroxybenzoyl)]glucopyranoside (8), were isolated together with three known naphthalenyl glucopyranosides (2, 3 and 5), one alpha-tetralonyl glucopyranoside (6), four flavonoids (9-12), and two galloyl glucopyranosides (13, 14). Amongst the isolated compounds, 1,2,6-trigalloylglucopyranose (13) and 1,2,3,6-tertagalloylglucopyranose (14) exhibited the most potent inhibition of reverse transcriptase (RT) activity with IC50 values of 0.067 and 0.040 microM, respectively, while the latter compound also inhibited ribonuclease H (RNase H) activity with an IC50 of 39 microM, comparable in potency to illimaquinone used as a positive control. 1,4,8-Trihydroxy-naphthalene 1-O-beta-D-glucopyranoside (2), 1,4,8-trihydroxynaphthalene 1-O-beta-D-[6'-O-(4"-hydroxy-3",5"-dimethoxybenzoyl)]glucopyranoside (3) and 8 showed moderate inhibition against both enzyme activities, and inhibitory potency of 2 against RNase H activity (IC50 = 156 microM) was slightly greater than that against the RT activity (IC50 = 290 microM). The inhibitory potencies of 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(4"-hydroxy-3",5"-dimethoxybenzoyl)] glucopyranoside (6), 7 and 8 against RT activity increased accompanied by an increase in the number of free hydroxyls on the galloyl residues, as represented by the IC50 values of > 500, 330 and 5.8 microM, respectively.