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 glucopyrano sides, I,4,8-trihydroxynaphthalene 1-O-[alpha-L-arabinofuranosyl-(1-->6)-be ta-D-glucopyranoside] (1) and 1,4,8-trihydroxynaphthalene 1-O-beta-D-[6'-O- (3",5"-dihydroxy-4"-methoxybenzoyl)]glucopyranoside (4), and two new alpha- tetralonyl glucopyranosides, 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-bet a-D-[6'-O-(3",5"-dihydroxy-4"-methoxybenzoyl)] glucopyranoside (7) and 4 al pha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(3",4'',5"-trihydroxybe nzoyl)] (8), were isolated together with three known naphthalenyl glucopyra nosides (2, 3 and 5), one alpha-tetralonyl glucopyranoside (6), four flavon oids (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 re reverse transcriptase (RT) activity with IC50 values of 0.067 and 0.040 mu M, respectively; while the latter compound also inhibited ribonuclease H (RNase H) activity with an IC50 of 39 mu M, comparable in potency to illim aquinone used as a positive control. 1,4,8-Trihydroxy-naphthalene 1-O-beta- D-glucopyranoside (2), 1,4,8-trihydrosynaphthalene 1-O-beta-D-[6'-O-(4"-hyd roxy-3",5"-dimethoxybenzoyl)] copyranoside (3) and 8 showed moderate inhibi tion against both enzyme activities, and inhibitory potency of 2 against RN ase H activity (IC50=156 mu M) was slightly greater than that against the R T activity (IC50=290 mu M) The inhibitory potencies of 4 alpha,5,8-trihydro xy-alpha-tetralone 5-O-beta-D-[6'-O-(4"-hydroxy-3",5"-dimethoxybenzoyl)] gl ucopyranoside (6), 7 and 8 against RT activity increased accompanied by an increase in the number of free hydroxyls on the galloyl residues, as repres ented by the IC50 values of >500, 330 and 5.8 mu M, respectively.