新型糖苷类衍生物降糖作用筛选和研究  

Screening and research on hypoglycemic effects of novel glycoside derivatives

作　　者：王小彦[1,2] 王玉丽[1] 陈娇[3] 赵桂龙[1] 徐为人[1] 汤立达[1] 

机构地区：[1]天津药物研究院天津市新药设计与发现重点实验室,天津300193 [2]天津中医药大学研究生院,天津300193 [3]天津医科大学基础医学院,天津300070

出　　处：《中草药》2013年第4期454-458,共5页Chinese Traditional and Herbal Drugs

基　　金：国家重大新药创制专项(2011ZX09401-009);国家重大创制专项(2011ZX9401-009);天津市科技支撑计划重点项目(10ZCKFSH01300)

摘　　要：目的针对钠-葡萄糖协同转运蛋白抑制剂(SGLT)靶点,通过尿糖检测方法筛选和评价糖苷类衍生物的降糖作用。方法 SD大鼠分别单次ig给予8个新型糖苷类衍生物30 mg/kg,在不同时段收集大鼠的尿液,己糖激酶法测定葡萄糖的量;尾静脉取血,血糖仪测血糖水平;同时对活性化合物进行大鼠糖耐量实验。结果新型糖苷类衍生物中N-糖苷类化合物TY702-1N和S-糖苷类化合物TY702-1S对大鼠ig葡萄糖水溶液后的排糖作用较弱,C-糖苷类化合物TY702-4C的排糖作用较强,且显示剂量相关性。结论就开发和研制作用强、药动学性质好的降糖药物而言,新型糖苷类衍生物TY702-4C是一个具有较好前景的先导化合物。Objective Aiming at the target point of sodium-glucose transport protein （SGLT） inhibitors, to screen and estimate the hypoglycemic effects of novel glycoside derivatives by urine glucose testing methods. Methods SD rats were ig administered with eight novel glycoside derivatives （30 mg/kg）; The urine of rats was collected and the content of glucose was measured by hexokinase method in various periods. Also, the blood samples were obtained from tail vain of rats, the blood glucose was measured using blood glucose meter, and the glucose tolerance test of the active compounds was carried out. Results In novel glycoside derivatives, N-glycoside TY702-1N and S-glycoside TY702-1S had less hypoglycemic effect, C-glycoside TY702-4C had more obvious effect of excreting glucose, and it has a dose-dependent manner in blood glucose and urine gluose. Conclusion TY702-4C is a lead compound with good prospect in the research and development of new drug with more efficient and better pharmacokinetic eharacteristics.

关 键 词：糖苷类衍生物 降糖作用 钠-葡萄糖协同转运蛋白抑制剂 尿糖 血糖 糖耐量 

分 类 号：R965.1[医药卫生—药理学] R977.15[医药卫生—药学]