You Zhong-Lu, Shi Da-Hua, Xu Chen, Zhang Qiang, Zhu Hai-Liang
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Eur J Med Chem. 2008 Apr;43(4):862-71. doi: 10.1016/j.ejmech.2007.06.015. Epub 2007 Jul 10.
Twenty transition metal complexes with Schiff bases were evaluated for their inhibitory activities on xanthine oxidase (XO), of which 11 were newly synthesized and characterized by X-ray single crystal diffraction. It was found that 9 of the 20 complexes showed potent inhibitory activities against XO near to the standard inhibitor allopurinol. The cadmium(II) complex (8) had the most potent inhibitory activity with the IC(50) value of 2.16 microM. Relationships between the structures and the activities showed that the ligands and the metal ions influenced the inhibitory activities. The XO inhibition of the Schiff base metal complexes most probably resulted from their direct interactions with the enzymes "in the whole complex form". These results demonstrated that the Schiff base transition metal complexes could be potential selective XO inhibitors.
对20种含席夫碱的过渡金属配合物进行了黄嘌呤氧化酶（XO）抑制活性评估，其中11种为新合成的，并通过X射线单晶衍射进行了表征。结果发现，20种配合物中有9种对XO表现出与标准抑制剂别嘌呤醇相近的强效抑制活性。镉（II）配合物（8）具有最强的抑制活性，IC（50）值为2.16微摩尔。结构与活性之间的关系表明，配体和金属离子会影响抑制活性。席夫碱金属配合物对XO的抑制作用很可能源于它们以“整个配合物形式”与酶的直接相互作用。这些结果表明，席夫碱过渡金属配合物可能是潜在的选择性XO抑制剂。
