Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effec...Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effects in the gastrointestinal tract. The principle of bioisosterism was applied to design derivatives replacing the carboxylic acid group. The carboxylic acid group was replaced with bioisoteric groups, such as 1,2,4-triazole-3-thiol and hydroxamic acid. The derivatives were then synthesized, characterized, and evaluated in rats for reduced gastrointestinal irritation and hypolipidemic effects. Gemfibrozil was used as standard for comparison. The derivatives demonstrated less gastric irritation and retained hypolipidemic effects, however the hypolipidemic affects were significantly less than that of Gemfibrozil. The results of this study offers a direction for further research on the application of bioisosterism for the design of new derivatives of Gemfibrozil and other fibric acid derivatives.展开更多
吉非罗齐(gemfibrozil)是一种药物类新污染物,对水生生物的神经系统可造成损害,其在水环境中的普遍存在,可能对中国水生生态系统构成潜在风险,但针对吉非罗齐的水质基准及生态风险评估尚缺乏系统研究。本研究基于ECOTOX、Web of Scienc...吉非罗齐(gemfibrozil)是一种药物类新污染物,对水生生物的神经系统可造成损害,其在水环境中的普遍存在,可能对中国水生生态系统构成潜在风险,但针对吉非罗齐的水质基准及生态风险评估尚缺乏系统研究。本研究基于ECOTOX、Web of Science和中国知网等相关数据库,收集整理了吉非罗齐对中国淡水生物的毒性数据,筛选出的急性数据涵盖5门5科7个物种,最敏感物种为水螅(Hydra vulgaris);慢性毒性数据涵盖4门6科10个物种,最敏感物种为斑马鱼(Danio rerio)。按照物种敏感度分布法推导出中国吉非罗齐的短期基准为1431.3μg·L^(-1)、长期基准为14.4μg·L^(-1)。收集了中国近20年地表水及污水处理厂尾水中吉非罗齐的暴露浓度数据共计583条,浓度范围在0~490 ng·L^(-1)。使用概率密度法和风险商评估法对其进行了生态风险评估,概率密度面积范围在1.8×10^(-5)~3.3×10^(-3);RQ值范围在0~0.034,结果表明吉非罗齐在中国地表水中的生态风险整体较低。研究成果可为吉非罗齐的水质标准制定和环境风险管理提供参考依据。展开更多
The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectru...The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectrum. The results showed that a 1 ： 1 （β-CD ： gemfibrozil） complex was formed with an apparent association constant of 3.844 × 10^3 L·mol^-1. Based on the enhancement of the fluorescent intensity of gemfibrozil, a spectrofluorimetric method for the determination of gemfibrozil in bulk aqueous solution in the presence of β-CD was developed. The linear range was 3.30 ng·mL^- 1 -6.00 ug·mL^-1 with the detection limit of 0.980 ng·mL^-1. There was no interference from the excipients normally used in tablet composition and the serum main compositions. The proposed method was then successfully applied to the determination of gemfibrozil in capsules and serum.展开更多
文摘Gemfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits; however, the presence of a carboxylic acid moiety in its structure is responsible for side effects in the gastrointestinal tract. The principle of bioisosterism was applied to design derivatives replacing the carboxylic acid group. The carboxylic acid group was replaced with bioisoteric groups, such as 1,2,4-triazole-3-thiol and hydroxamic acid. The derivatives were then synthesized, characterized, and evaluated in rats for reduced gastrointestinal irritation and hypolipidemic effects. Gemfibrozil was used as standard for comparison. The derivatives demonstrated less gastric irritation and retained hypolipidemic effects, however the hypolipidemic affects were significantly less than that of Gemfibrozil. The results of this study offers a direction for further research on the application of bioisosterism for the design of new derivatives of Gemfibrozil and other fibric acid derivatives.
基金Project supported by the Program for New Century Excellent Talents in University （No. NCET-04-0651）, the National Natural Science Foundation of China （Nos. 20335030 and 20575036） and the Important Project of Natural Science Foundation of Shandong Province of China （No. Z2003B01）.
文摘The supramolecular interaction of gemfibrozil with β-cyclodextrin （β-CD） was studied by spectrofluorimetry. The mechanism of the inclusion was discussed by spectrofluoremetry, infrared spectrum and ^1H NMR spectrum. The results showed that a 1 ： 1 （β-CD ： gemfibrozil） complex was formed with an apparent association constant of 3.844 × 10^3 L·mol^-1. Based on the enhancement of the fluorescent intensity of gemfibrozil, a spectrofluorimetric method for the determination of gemfibrozil in bulk aqueous solution in the presence of β-CD was developed. The linear range was 3.30 ng·mL^- 1 -6.00 ug·mL^-1 with the detection limit of 0.980 ng·mL^-1. There was no interference from the excipients normally used in tablet composition and the serum main compositions. The proposed method was then successfully applied to the determination of gemfibrozil in capsules and serum.
