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在前期的研究中,我们将9-(4-氯苯氧羰基)-10-甲基吖啶酯三氟甲基磺酸盐(CPOCMA)用于测定血清芳香酯酶活性,取得满意结果.在此基础上,本文以CPOCMA为底物,建立化学发光法评估药物对芳香酯活性影响的新方法.以硝酸甘油为模型药物,比较了化学发光法与UV方法的一致性.并将此法应用于评价三种抗炎药吲哚美辛、阿司匹林和乙酰氨基酚对芳香酯酶活性的影响.药物的加入使血清催化CPOCMA水解的动力学减缓,这表明这些药物均为抑制剂.吲哚美辛、阿司匹林和乙酰氨基酚表现出的IC50值分别为0.254、0.564和0.656 mmol/L,抑制常数ki分别为0.154、1.38和2.98 mmol/L.加入药物后的Lineweaver-Burk曲线表明这三种药物对PON的抑制均为竞争性抑制.根据加入药物后的动力学曲线,其IC50值、抑制常数和米氏常数的变化均表明这三种药物的抑制能力大小顺序:吲哚美辛>阿司匹林>乙酰氨基酚.CPOCMA可以作为PON底物体外评价药物对PON的抑制能力和抑制机理.UV法不适合评价紫外吸收峰与UV法的检测波长重叠的药物,而新建立的化学发光法对这类药物的筛选有独特优势.
In the previous study, we used 9- (4-chlorophenoxycarbonyl) -10-methylacridine trifluoromethanesulfonate (CPOCMA) for the determination of serum aroma esterase activity with satisfactory results. At Based on this, CPOCMA was used as a substrate to establish a new method of chemiluminescence to evaluate the effect of drugs on the activity of aromatic esters.Using nitroglycerin as a model drug, the consistency of chemiluminescence and UV methods was compared and the method was applied To evaluate the effect of three antiinflammatory drugs, indomethacin, aspirin and acetaminophen on aromatase esterase activity, the pharmacokinetics of serum-catalyzed CPOCMA hydrolysis was reduced by the addition of the drug, indicating that these drugs are inhibitors Simvastatin, aspirin and acetaminophen showed IC50 values of 0.254, 0.564 and 0.656 mmol / L, respectively. The inhibition constants ki were 0.154, 1.38 and 2.98 mmol / L, respectively. The Lineweaver-Burk curves after drug addition showed that the three drugs Inhibition of PON are competitive inhibition.According to the kinetic curve after drug addition, the change of IC50 value, inhibition constant and Michaelis constant indicated the order of inhibition of these three drugs: indomethacin> aspirin> Acetaminophen .CPOCMA Can be used as PON substrate in vitro evaluation of drug inhibition of PON and inhibition mechanism.UV method is not suitable for evaluation of UV absorption peak and UV detection wavelength overlapping drugs, and the newly established chemiluminescence method for screening of such drugs unique Advantage.