Synthesis,Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring b-Amyrenone

Urease enzyme(UE)has been reported to be a potent virulence factor for Helicobacter pylori(HP)bacteria indicated to be responsible for various gastrointestinal diseases.Therefore,the spread of HP,currently regarded by the World Health Organization as a class 1 carcinogen,could be better controlled by targeting UE.It is in this line that we have synthesized three new derivatives(2–4)of the naturally occurring olean-12-en-3-one(1),which was previously isolated from the figs of Ficus vallis-choudae Delile(Moraceae).Among the synthesized compounds,3 and 4 contain an indole moiety.Their structures were unambiguously assigned by spectroscopic and spectrometric techniques(1D-NMR,2D-NMR and MS).The starting material and the synthesized compounds were screened for UE inhibition activity,and showed significant activities with IC50 values ranging from 14.5 to 24.6 lM,with compound(1)being the most potent as compared to the positive control thiourea(IC50=21.6 lM).Amongst the synthetic derivatives,compound 4 was the most potent(IC50-=17.9 lM),while the others showed activities close to that of the control.In addition,molecular docking study of target compounds 2–4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

雷山石杉的化学成分研究

目的研究雷山石杉的化学成分。方法使用制备薄层、硅胶柱色谱、SephadexLH-20及半制备高效液相色谱法等手段进行分离、纯化，结合文献资料、理化性质、1H—NMR及13C-NMR数据进行结构鉴定。结果分离得到10个化合物，分别鉴定为（15R）-12，16-epoxy-11，14-dihydroxy-8，11，13-abietatrien-7-one（Ⅰ），21-epi—serratenediol-3，21-acetate（Ⅱ），setTatene—diol-3-acetate（Ⅲ），21-epi—serratenediol-3-acetate（Ⅳ），21a—hydroxy—serrat-14-en-3β-ol（Ⅴ），21β-hydroxy—serrat-14-en-3β-ol（Ⅵ），石杉碱甲（huperzineA，Ⅶ），蔗糖（Ⅷ），β-谷甾醇（Ⅸ），胡萝卜串（Ⅹ）。结论化合物Ⅰ～Ⅹ均首次从该植物中分离到。