The Synthesis, Structure and Activity Evaluation of Secnidazole Derivatives as Helicobacter pylori Urease Inhibitors

Xi-Shou      Huang; Kai      Liu; Yong      Yin; Wan-Mei      Li; Wei      Ran; Man      Duan; Li-Sheng      Wang; Hai-Liang      Zhu

Abstract

Thirty secnidazole derivatives have been synthesized and evaluated for Helicobacter pylori (H. Pylori) urease inhibitory activities and anti-inflammatory activities. All of them were reported for the first time. Their chemical structures were characterized by 1H NMR, 13C NMR, MS, and elemental analysis. Compound 5a, 6c and 8c showed the most potent urease inhibitory activities and anti-inflammatory activities with IC50 values of 1.7 μM, 1.0 μM, 2.0 μM and inhibition of 62.60%, 59.54%, 71.76%, respectively. Docking simulation was performed to position compound 6c into the urease active site to determine the probable binding model. Compound 5a, 6c and 8c with potent inhibitory activity against H. pylori may be potential antibacterial agents.

Keywords: Urease inhibitors, Helicobacter pylori, secnidazole derivatives, salicyclic acid derivatives, anti-inflammatory activites, docking, antibacterial agent, urea hydrolase, gastroduodenal diseases, living organisms