磺酰脲衍生物金属配合物的降血糖作用研究

Study of sulphonylureas derivative ligand and its metal complexes on hypoglycemic activity

目的:对10个磺酰脲衍生物金属配合物的降血糖作用进行初步筛选。方法:正常小鼠灌胃给药后,剪尾取血,用葡萄糖氧化酶-过氧化物酶(GOD-PAP)法测定血糖,以甲苯磺丁脲(D860)作为阳性对照药物,分析它们的降血糖作用,探讨其作用机理及化学结构与降血糖作用的构效关系。结果:实验表明,ZnL2.2H2O、NdL3.2H2O、SmL3.2H2O、Zn(HL')2.2NO3、Eu(HL')3.3NO3、HL、HL'等7个化合物,均具有降低正常小鼠血糖的活性,而EuL3.2H2O、Nd(HL')3.3NO3、Sm(HL')3.3NO3降糖活性不明显。结论:HL在2h对正常小鼠的降血糖活性强于D860,提示对甲苯磺酰脲1位取代基为脂环基(环己基)时,其降血糖活性高于直链脂基(丁基),更高于杂环基团(4-安替比林基)。

AIM：To screen the hypoglycemic activity of diferent sulphonylureas derivative ligand and their metal complexes. METHODS：The mice were administered intragastrically,the blood samples were obtained from tail vein. The serum glucose levels were determined by glucose-oxidase-peroxidase （GOD-PAP） method. The hypoglycemic activities were analyzed by the mean of tolbutamide as a positive control drug,and its mechanism and structure-activity relationship between chemical structure and hypoglycemic activity were studied. RESUITS：The results showed that ZnL2·2H2O,NdL3·2H2O,SmL3·2H2O,Zn（HL＇）2·2NO3,Eu（HL＇）3·3NO3,HL and HL＇ all reduced the blood sugar in normal mice,while EuL3·2H2O,Nd（HL＇）3·3NO3 and Sm（HL＇）3·3NO3 had no obvious hypoglycemic activity. CONCLUSION：The hypoglycemic activity of HL is stronger than that of tolbutamide in normal mice at 2 h,indicating that when the first substituent of tosylurea is the alicyclic group （cyclohexyl）,its hypoglycemic activity may be higher than the straight-chain lipid group （butyl）,and much higher than the heterocyclic group （4-antipyrine）.