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...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.展开更多
基金BKJJ acknowledges The World Academy of Sciences(TWAS)and the International Center for Chemical and Biological Sciences(ICCBS),University of Karachi,Pakistan for their financial and technical support through the ICCBS-TWAS Postdoctoral Fellowship number 3240280476CVS also acknowl-edges financial support from the German Academic Exchange Ser-vices(DAAD)for doctoral candidates.
文摘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.
