Molecular docking, kinetics study, and structure-activity relationship analysis of quercetin and its analogous as Helicobacter pylori 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 IC(50) 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.
College of Chemistry and Chemical Engineering, and Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, P. R. China. xiaozhuping2005@163.com
Zhu-Ping
ZP
Xiao
Xu-Dong
XD
Wang
Zhi-Yun
ZY
Peng
Shen
S
Huang
Pan
P
Yang
Qing-Shan
QS
Li
Li-Hu
LH
Zhou
Xiao-Jun
XJ
Hu
Li-Jun
LJ
Wu
Yin
Y
Zhou
Hai-Liang
HL
Zhu
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D011794:Quercetin / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D011794:Quercetin; D014510:Urease