Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors
Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors
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幽门螺杆菌脲酶抑制剂甲硝唑衍生物的合成、分子对接及生物学评价
DOI：
10.1016/j.bmc.2009.09.018
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发表时间：
2009-11-01
影响因子：
3.5
通讯作者：
Zhu, Hai-Liang
中科院分区：
文献类型：
--
作者：
Mao, Wen-Jun;Lv, Peng-Cheng;Zhu, Hai-Liang
通过甲硝唑与水杨酸衍生物的偶联反应，合成了14个甲硝唑衍生物（化合物3a-f和4 b-h）。所有这些都是首次报道。它们的化学结构通过H-1 NMR、MS和元素分析表征。体外抗幽门螺杆菌尿素酶活性的研究表明，许多化合物具有潜在的抑制幽门螺杆菌的活性。幽门螺杆菌尿素酶。化合物4 b（IC 50 = 26 μ M）和4g（IC 50 = 12 μ M）的效果与乙酰异羟肟酸（一种众所周知的H.幽门螺杆菌尿素酶抑制剂用作阳性对照。IC_（50）实验结果表明，该抑制剂是一种有效的脲酶抑制剂。利用AUTODOCK 4.0程序进行对接分析，可以解释化合物4g对H.幽门螺杆菌尿素酶。(C)2009爱思唯尔有限公司保留所有权利。
Fourteen metronidazole derivatives (compounds 3a-f and 4b-h) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by H-1 NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC50 = 26 mu M) and 4g (IC50 = 12 mu M) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC50 showed that inhibitor was potent urease inhibitor. A docking analysis using the AUTODOCK 4.0 program could explain the inhibitory activities of compound 4g against H. pylori urease. (C) 2009 Elsevier Ltd. All rights reserved.