中文摘要：

根据基质金属蛋白酶（MMPs）的活性位点附近三维空间结构，设计合成了4种双膦酸类化合物，利用酶促反应动力学方法对比测试了双膦酸化合物及阿伦磷酸钠（Alendronate）对MMPs的抑制效果；结合分子对接方法以及荧光滴定光谱研究了双膦酸化合物与MMPs的分子识别和作用机理，并得到了二者的结合模型．

英文摘要：

Matrix metalloproteinases（ MMPs）, a group of zinc-dependent metalloproteinases, are responsible for the hydrolytic breakdown of extracellular matrix. Aberrantly over expression of MMPs has been associated with much human pathology including cancer, arthritis, and heart disease etc. Therefore, the development of MMPs inhibitors to drugs has always been of great interest to scientific institutions. Bisphosphonates were reported to be a new kind of MMPs inhibitors with great potential. According to the 3-dimensional structure, 4 bisphosphonates are designed, synthesized and tested against several typical MMPs. The inhibitory activities toward MMP-2, MMP-3 and MMP-9 were tested in vitro using flourometrie method. The results show micromolar-level activity and modest selectivity toward MMPs. Molecular docking study and fluorometic titration spectra were performed to reveal the recognition and inhibition mechanism between MMPs and bisphosphonates, and the binding mode between them was proposed.