细胞膜色谱法筛选噻唑烷酸酯类化合物活性

 目的应用细胞膜色谱法(cell membrane chromatography,CMC)对实验室合成的10种取代噻唑烷酸酯类化合物进行活性筛选。方法细胞膜色谱筛选条件:心肌细胞膜色谱柱(2 mm×50 mm);流动相为25 mmol·L-1磷酸盐缓冲液,pH7.4;柱温37℃;流速0.3 mL·min^-1,不同波长下检测,以容量因子、保留时间等为指标,卡托普利(captopril)为阳性对照,根据化合物在细胞膜色谱柱上的保留特性判断其亲和活性的大小。并通过大鼠降压实验测定了化合物的降压作用。结果10种噻唑烷酸酯类化合物除2-(4-氯苯基)-噻唑烷-4-酸乙酯外,均在心肌细胞膜色谱柱上有特异性吸附,说明这些化合物均具有一定生理活性。进一步降压实验表明,除2-(4-二甲氨基苯基)-噻唑烷-4-羧酸乙酯、2-(3-硝基苯基)-噻唑烷-4-羧酸乙酯、2-(4-氯苯基)-噻唑烷-4-酸乙酯外均具有显著的降压作用(P<0.05)。结论细胞膜色谱法可作为一种定性的、初步筛选化合物的快速方法。部分取代噻唑烷酸酯类化合物能吸附于心肌细胞膜表面,并具有降压作用。

Activity Screen of Thiazolidine-4-Carboxylic Acid Ethyl Ester by Cell Membrane Chromatography

OBJECTIVE To screen the activity of thiazolidine-4-carboxylic acid ethyl ester with cell membrane chromatography(CMC).METHODS The conditions of CMC consisted of cardiac muscle CMC column(50 mm×2 mm) at 37 ℃.The mobile phase was 25 mmol·L^-1 phosphate buffer(pH 7.4) at the flow-rate of 0.30 mL·min^-1.Captopril was used as positive control in the screening.The capacity factors or retention time was used as the chromatographic parameters.The pharmacological effect of compounds was tested by the antihypertensive experiment in SD rats.RESULTS The compounds,except 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid ethyl ester,were adsorbed well on cell membrane stationary phase.It was indicated these compounds had physiological activities.The antihypertensive activity of compounds determined in rats showed the compounds,except 2-(4-dimethylamino-phenyl)-thiazolidine-4-carboxylic acid ethyl ester,2-(3-nitro-phenyl)-thiazolidine-4-carboxylic acid ethyl ester and 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid ethyl ester,had antihypertensive activity.CONCLUSION The interactions between the compounds and the membrane or membrane receptor were reflected in the cardiac muscle CMC model.The CMC could be used as a good method of qualitative analysis and screen.Most of synthesized compounds could be adsorbed well on cell membrane and had antihypertensive effect.