Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros lotus

来源 :Chinese Journal of Natural Medicines | 被引量 : 0次 | 上传用户:zhoujhipanel
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Two new dimeric naphthoquinones, 5′,8′-dihydroxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone(1; Di-naphthodiospyrol D) and 5′,8′-dihydroxy-5,8-dimethoxy-6,6′-dimethyl-7,3′-binaphthyl-1,4,1′,4′-tetraone(2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin(3) and 8-hydroxy diospyrin(4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were evaluated for urease activity and phosphodiesterase-Ⅰ, carbonic anhydrase-Ⅱ and α-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their corresponding fractions showed significant and selective inhibitory effects on urease activities. The IC_(50) values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 μmol·L-1, respectively, using thiourea(IC_(50) = 21 ± 0.11 μmol·L~(-1)) as the standard inhibitor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition. Two new dimeric naphthoquinones, 5 ’, 8’-dihydroxy-6,6’-dimethyl-7,3’-binaphthyl- 1,4,1’, 4’-tetraone (Di- naphthodiospyrol D) and 5 ’ 8’-dihydroxy-5,8-dimethoxy-6,6’-dimethyl-7,3’-binaphthyl- 1,4,1 ’, 4’-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin Their structures were elucidated by advanced spectroscopic analyzes including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1 and 2 and their counter-abundant effects on urease activities. Compounds 1 and 2 and α-chymotrypsin enzyme inhibitory activities. Compounds IC_ (50) values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 μmol·L-1, respectively, using thiourea (IC 50 = 21 ± 0.11 μmol·L -1) as the standard inhibi tor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition.
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