细胞膜色谱初步测定2-取代噻唑烷-4-羧酸活性

Activity determination of 2-substituted thiazolidine-4-carboxylic acid by cell membrane chromatography

测定合成的2-取代噻唑烷-4-甲酸的初步生理活性.将由动物心脏制备的心肌细胞膜与硅胶结合制备成心肌细胞膜硅胶混悬液,湿法填充色谱柱(50mm×2mm I.D.)得到细胞膜色谱固定相,同时将硅胶填充至同样色谱柱得到阴性对照硅胶固定相.以卡托普利为阳性对照药物,磷酸盐缓冲液(pH7.4)为流动相,在37℃,流速0.5mL/min,不同波长下检测.结果显示2-(4-羟基苯基)-噻唑烷-4-甲酸(HT)、2-丙基-噻唑烷-4-甲酸(PT)、2-(4-羟基13-甲氧基苯基)-噻唑烷-4-甲酸(HMT)及卡托普利在细胞膜色谱柱上均有吸附,而在硅胶柱上无特异性吸附.表明化合物能与细胞膜产生特异性结合,初步判断HT,PT,HMT具有生理活性.细胞膜色谱用于定性测定化合物活性简便、快捷、准确.

To screen the activity of 2-substituted thiazolidine-4-carboxylic acid, cell membrane chromatography （CMC） was used. The cardiac muscle CMC column （50 mm×2 mm I.D.） with phosphate buffer （pH 7.4） as mobile phase was used for analysis. The flow rate of mobile phase was 0.50 mL/min and the column temperature was 20℃. Different compounds had different detective UV wavelength. The silica column was used for comparative analysis. Captopril was used as positive control in the screen. The retention times and calculated capacity factors, as chromatographic parameters, were recorded carefully. The results showed that 2-（4-hydroxylphenyl）-thiazolidine-4-carboxylic acid （HT）, 2-propyl-thiazolidine-4-carboxylic acid （PT）, 2-（4-hydroxyl-3-methoxylphenyl）-thiazolidine-4-carboxylic acid （HMT） and captopril were adsorbed well in cell membrane stationary phase while the compounds were not adsorbed in silica stationary phase. The interactions between the compounds and the membrane or membrane receptor were reflected in the cardiac muscle CMC model. HT, PT, HMT have physiological activity. CMC can be used as a good method to qualitative analysis and screening.