期刊
CHEMISTRYSELECT
卷 5, 期 15, 页码 4580-4587出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/slct.202000578
关键词
Cyclization; Induced fit docking; Inhibitors; 1,3,4-Oxadiazole; Pantoprazole; Urease active site flap
资金
- National Institute for Medical Research Development (NIMAD) [982736]
- Research Council of Tehran University of Medical Sciences
A number of pantoprazole derivatives were synthesized and screened for their urease inhibitory properties. Some of them showed potent inhibitions against jack bean urease. All compounds showed varying degree of IC50 in the range of 25.85 to 181 mu Mol as compared to standard acetohydroxamic acid (AHA) (100 +/- 2.02 mu Mol). Derivatives bearing 5-aryl-1,3,4-oxadiazole ring substitutions (aryl= pyrazyl, pyridyl and phenyl) were found to be more potent inhibitors than AHA and pantoprazole. The most promising compound, 2-((3,4-dimethoxypyridin-2-yl)methylthio)-5-(pyrazin-2-yl)-1,3,4-oxadiazole 12, with IC50 value of 25.85 +/- 1.21 showed remarkable urease inhibition activity. In silico molecular modeling investigation performed to rationalize the possible binding interaction and ADME properties of compounds over the active site of urease enzyme. The induced fit docking study showed that compound 12 interacted with conserved residues His593 and Arg609 located at the mouth of the urease active site flap and are essential for enzyme catalytic activity. These target compounds could be further studied as a lead skeleton for discovery of novel urease inhibitors.
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