Shatemirova K K, Davydova G A, Verevkina I V, Tichilkin A I
Vopr Med Khim. 1977 Sep-Oct;23(5):609-18.
New derivatives of 2-propinyl amine were studied as possible inhibitors of mitochondrial monoamine oxidases (MAO) from rat liver and brain tissues. Kinetics of inhibition of the MAO activity (A and B types) is described for one of the substances studied -- N-(8-quinolyl methyl)-N-methyl-2-propinyl amine. Interaction of N-(8-quinolylmethyl)-N-methyl-2-propinyl amine with MAO of the A type (serotonin as a substrate) and of the B type (beta-phenylethylamine as a substrate) was studied by the kinetic method, which enabled to determine and quantitatively estimate the steps of enzyme-inhibitor complexes formation. The inhibition of the mitochondrial MAO A and B types by the substance was shown to include the steps of formation of dissociating enzyme-inhibitor intermediates with the subsequent irreversible modification of them. The data on K1 values, estimated in experiments with serotonin and beta-phenylethylamine as substrates, show that the affinity of N-(8-quinolyl methyl)-N-methyl-2-propinyl amine towards MAO of the A type was 10-fold higher than the affinity towards MAO of the B type. The rates of these complexes conversion into irreversibly blocked forms of the MAO A and B types was found to be similar.
对2-丙炔胺的新衍生物作为大鼠肝脏和脑组织中线粒体单胺氧化酶(MAO)潜在抑制剂进行了研究。描述了所研究的一种物质——N-(8-喹啉基甲基)-N-甲基-2-丙炔胺对MAO活性(A和B型)的抑制动力学。采用动力学方法研究了N-(8-喹啉基甲基)-N-甲基-2-丙炔胺与A型MAO(以血清素为底物)和B型MAO(以β-苯乙胺为底物)的相互作用,该方法能够确定并定量评估酶-抑制剂复合物形成的步骤。结果表明,该物质对线粒体MAO A型和B型的抑制作用包括形成解离的酶-抑制剂中间体并随后对其进行不可逆修饰的步骤。以血清素和β-苯乙胺为底物的实验中估算的K1值数据表明,N-(8-喹啉基甲基)-N-甲基-2-丙炔胺对A型MAO的亲和力比对B型MAO的亲和力高10倍。发现这些复合物转化为MAO A型和B型不可逆阻断形式的速率相似。