磺酰脲衍生物金属配合物的降血糖作用研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (5): 507-510.

磺酰脲衍生物金属配合物的降血糖作用研究

董淑弘¹, 谢国强², 张宝来¹, 高明堂¹, 吴勇杰¹, 曾正志²

¹兰州大学基础医学院药理学研究所,甘肃省新药临床前研究重点实验室,²兰州大学化学化工学院,兰州 730000,甘肃

收稿日期:2010-01-29 修回日期:2010-05-12 出版日期:2010-05-26 发布日期:2020-09-16
通讯作者: 吴勇杰,男,教授,硕士研究生导师,研究方向:新药药理学。Tel: 13893445805 E-mail: wuyj@lzu.edu.cn
作者简介:董淑弘,女,助理研究员,研究方向:新药药理学。Tel: 13993143915 E-mail: dongshh@lzu.edu.cn

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

DONG Shu-hong¹, XIE Guo-qiang², ZHANG Bao-lei¹, GAO Ming-tang¹, WU Yong-jie¹, ZENG Zheng-zhi²

¹Department of Pharmacology, School of Basic Medical Science of Lanzhou University, Key Laboratory of Preclinical of New Traditional Chinese Medicines of Gansu Province, ²College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000,Gansu, China

Received:2010-01-29 Revised:2010-05-12 Online:2010-05-26 Published:2020-09-16

摘要/Abstract

摘要： 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 2 h 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)。

关键词: 1-环已基-3-对甲苯磺酰脲, 1-(4-安替比林)-3-对甲苯磺酰脲, 磺酰脲衍生物金属配合物, 降血糖作用, 构效关系

Abstract: 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).

Key words: 1-cyclohexyl-3-tosylurea, 1-(4-antipyrine)-3-tosylurea, Sulphonylureas derivative metal complexes, Hypoglycemic activity, Structure-activity relationship

中图分类号:

R965

董淑弘, 谢国强, 张宝来, 高明堂, 吴勇杰, 曾正志. 磺酰脲衍生物金属配合物的降血糖作用研究[J]. 中国临床药理学与治疗学, 2010, 15(5): 507-510.

DONG Shu-hong, XIE Guo-qiang, ZHANG Bao-lei, GAO Ming-tang, WU Yong-jie, ZENG Zheng-zhi. Study of sulphonylureas derivative ligand and its metal complexes on hypoglycemic activity[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(5): 507-510.

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