Li Huan-Qiu, Xiao Zhu-Ping, Yan Tao, Lv Peng-Cheng, Zhu Hai-Liang
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Eur J Med Chem. 2009 May;44(5):2246-51. doi: 10.1016/j.ejmech.2008.06.001. Epub 2008 Jun 11.
Twenty amines and oximes from deoxybenzoins were prepared and evaluated for their inhibitory activity against Helicobacter pylori urease. Among these compounds, high inhibitory activities were observed in amines and oximes, especially amines 1b (IC(50)=0.011 mM) and 6b (IC(50)=0.047 mM) exhibited good in vitro activities, and were comparable to acetohydroxamic acid (AHA). The hydroxyl groups on deoxybenzoin skeleton may be responsible for the inhibitory activity and coordinate with the nickel (active site) on enzyme. A direct interaction may exist between the OH group of hydroxylamines or NH group of amines and His alpha323 of H. pylori urease, which is on the flap of the enzyme active site.
制备了20种源自脱氧安息香的胺类和肟类化合物，并评估了它们对幽门螺杆菌脲酶的抑制活性。在这些化合物中，胺类和肟类表现出较高的抑制活性，尤其是胺类化合物1b（IC(50)=0.011 mM）和6b（IC(50)=0.047 mM）具有良好的体外活性，且与乙酰氧肟酸（AHA）相当。脱氧安息香骨架上的羟基可能是抑制活性的原因，并与酶上的镍（活性位点）配位。羟胺的OH基团或胺类的NH基团与幽门螺杆菌脲酶位于酶活性位点侧翼的His α323之间可能存在直接相互作用。
