The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors.
Some pyrogallol and catechol derivatives were synthesized, and their urease inhibitory activity was evaluated by using acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor, as positive control. The assay results indicate that many compounds have showed potential inhibitory activity against H. pylori urease. 4-(4-Hydroxyphenethyl)phen-1,2-diol (2a) was found to be the most potent urease inhibitor with IC(50)s of 1.5±0.2 μM for extracted fraction and 4.2±0.3 μM for intact cell, at least 10 times and 20 times lower than those of AHA (IC(50) of 17.2±0.9 μM, 100.6±13 μM), respectively. This finding indicate that 2a would be a potential urease inhibitor deserves further research. Molecular dockings of 2a into H. pylori urease active site were performed for understanding the good activity observed.
Xiao
Zhu-Ping
ZP
Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, PR China. xiaozhuping2005@163.com
Ma
Tao-Wu
TW
Fu
Wei-Chang
WC
Peng
Xiao-Chun
XC
Zhang
Ai-Hua
AH
Zhu
Hai-Liang
HL
D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology*; D008958:Models, Molecular; D011748:Pyrogallol / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors*
D002396:Catechols; D004791:Enzyme Inhibitors; D011748:Pyrogallol; D014510:Urease; C034221:catechol