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Molecular Docking, Kinetics Study, and Structure–Activity Relationship Analysis of Quercetin and Its Analogous as Helicobacter pylori Urease Inhibitors

Xiao, Zhu-Ping, Wang, Xu-Dong, Peng, Zhi-Yun, Huang, Shen, Yang, Pan, Li, Qing-Shan, Zhou, Li-Hu, Hu, Xiao-Jun, Wu, Li-Jun, Zhou, Yin, Zhu, Hai-Liang
Journal of agricultural and food chemistry 2012 v.60 no.42 pp. 10572-10577
Helicobacter pylori, Lonicera japonica, inhibitory concentration 50, quercetin, stomach ulcers, structure-activity relationships, therapeutics, urease, urease inhibitors
It was disclosed in our group for the first time that the flavonoids in Lonicera japonica Thunb. are related to its therapy for gastric ulcer. Based on this finding, 20 flavonoids were selected for Helicobacter pylori urease inhibitory activity evaluation, and quercetin showed excellent potency with IC₅₀ of 11.2 ± 0.9 μM. Structure–activity relationship analysis revealed that removal of the 5-, 3-, or 3′-OH in quercetin led to a sharp decrease in activity. Thus, 3- and 5-OH as well as 3′,4′-dihydroxyl groups are believed to be the key structural characteristics for active compounds, which was supported by the molecular docking study. Meanwhile, the results obtained from molecular docking and enzymatic kinetics research strongly suggested that quercetin is a noncompetitive urease inhibitor, indicating that quercetin may be able to tolerate extensive structural modification irrespective of the shape of the active site cavity and could be used as a lead candidate for the development of novel urease inhibitors.