Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors

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.