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 (1)H 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 (IC(50)=26 microM) and 4 g (IC(50)=12 microM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC(50) showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4 g against H. pylori urease.
Mao
Wen-Jun
WJ
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Lv
Peng-Cheng
PC
Shi
Lei
L
Li
Huan-Qiu
HQ
Zhu
Hai-Liang
HL
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D016480:Helicobacter pylori / Q000201:enzymology*; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000378:metabolism
C545771:(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl4-methyl-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzoate; C545772:(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl5-bromo-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzoate; D000890:Anti-Infective Agents; D008795:Metronidazole; D014510:Urease