Molecular docking, kinetics study, and structure-activity relationship analysis of quercetin and its analogous as Helicobacter pylori urease inhibitors.
Molecular docking, kinetics study, and structure-activity relationship analysis of quercetin and its analogous as Helicobacter pylori urease inhibitors.
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DOI：
10.1021/jf303393n
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发表时间：
2012-10
影响因子：
6.1
通讯作者：
Zhu-Ping Xiao;Xu-dong Wang;Zhi-Yun Peng;Shen Huang;Pan Yang;Qingshan Li;Lihu Zhou;Xiao-jun Hu;Li‐jun Wu;Yin Zhou;Hailiang Zhu
中科院分区：
文献类型：
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作者：
Zhu-Ping Xiao;Xu-dong Wang;Zhi-Yun Peng;Shen Huang;Pan Yang;Qingshan Li;Lihu Zhou;Xiao-jun Hu;Li‐jun Wu;Yin Zhou;Hailiang Zhu
本课题组首次公开了金银花中总黄酮的含量。与其治疗胃溃疡有关。在此基础上，选择20种黄酮类化合物进行幽门螺杆菌脲酶抑制活性评价，槲皮素在IC（50）为11.2±0.9 μM时表现出良好的效价。构效关系分析表明，槲皮素中5-、3-或3'- oh的去除导致活性急剧下降。因此，3-和5-OH以及3',4'-二羟基被认为是活性化合物的关键结构特征，这得到了分子对接研究的支持。同时，分子对接和酶动力学研究结果强烈表明槲皮素是一种非竞争性脲酶抑制剂，这表明槲皮素可能能够耐受广泛的结构修饰，而不受活性位点空腔形状的影响，可以作为开发新型脲酶抑制剂的主要候选者。
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.