吡咯烷系列衍生物抑制蛋白降解酶活性的研究  

Protein Catabolic Enzymes Inhibitory Activities of Pyrrolidine Derivatives

作　　者：张丽[1] 徐文方[2] 张杰[2] 

机构地区：[1]青岛大学医学院药学系,山东青岛266021 [2]山东大学药学院,济南250012

出　　处：《中国药学杂志》2008年第6期469-471,共3页Chinese Pharmaceutical Journal

基　　金：教育部博士点基金项目(20060422029)

摘　　要：目的对合成的一系列吡咯烷衍生物,分别研究它们对2种蛋白降解酶——基质金属蛋白酶(MMP-2,MMP-9)和氨肽酶N(APN)的抑制情况。方法以琥珀酰明胶为底物,2,4,6-三硝基苯磺酸(TNBSA)为显色刺,测定化合物对明胶酶活性的影响;以L-亮氨酰对硝基苯胺为底物,测定化合物对APN的抑制活性。结果化合物A0,A8,A9,A10,B9和C10抑制明胶酶的活性较高,值得进一步进行体内试验研究。结论化合物对MMP-2,MMP-9的抑制活性高于对APN,说明所合成的吡咯烷系列衍生物虽然对这2种蛋白降解酶都有抑制活性,但是对MMP-2,MMP-9的选择性要优于对APN。OBJECTIVE To synthesis a series of pynolidine derivatives and study their inhibitory activities to two kinds of protein catabolic enzymes, matrix metallloproteinaes （ MMP-2, MMP-9 ） and aminopeptidase N （APN）. METHODS The inhibitory activities of these compound against gelatinase （ MMP-2 and MMP-9 ） were measured using succinylated gelatin as substrate and trinitro- benzenesulfonic acid （TNBSA） as developer, The inhibitory activities against aminopeptidase N（APN） were carried out with L-leucine p-nitroanilide as substrate, RESULTS Compound A0, A8, A9, A10, B9 and C10 showed high activities against gelatinase （MMP- 2 and MMP-9）, CONCLUSION Compound showed higher activities against gelatinase （MMP-2 and MMP-9 ） than to APN. It is shown that the selectivity of the compounds towards MMP-2, MMP-9 is higher than towards APN.

关 键 词：吡咯烷衍生物 基质金属蛋白酶抑制剂 氨肽酶N抑制剂 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]