Shirota F N, DeMaster E G, Elberling J A, Nagasawa H T
J Med Chem. 1980 Jun;23(6):669-73. doi: 10.1021/jm00180a018.
The relationship between metabolic depropargylation in vitro to inhibition of the low Km aldehyde dehydrogenase (AIDH) of rat liver mitochondria in vivo was determined for a number of compounds bearing a propargyl substituent on nitrogen or oxygen. Only those compounds which enzymatically released the highly reactive alpha, beta-acetylenic aldehyde, propioladehyde, when incubated in vitro with phenobarbital-induced rat liver microsomes, e.g., tripropargylamine (4), pargyline (1a), and N-propargylbenzylamine (1b), significantly elevated blood acetaldehyde levels when administered in vivo. Mitochondrial AIDH activity in these animals was corresponding reduced to less than or equal to 20% that of control animals. Compounds that did not inhibit mitochondrial AlDH activity to this degree did not produce significant levels of propiolaldehyde when incubated with microsomes. Thus, for this series of compounds, metabolic depropargylation is a requirement for AlDH inhibitory activity in vivo.
对于许多在氮或氧上带有炔丙基取代基的化合物，测定了其体外代谢去炔丙基化与体内对大鼠肝线粒体低 Km 醛脱氢酶（AIDH）抑制之间的关系。只有那些在体外与苯巴比妥诱导的大鼠肝微粒体一起孵育时能酶促释放高反应性的α，β - 乙炔醛（丙炔醛）的化合物，例如三丙炔胺（4）、帕吉林（1a）和 N - 炔丙基苄胺（1b），在体内给药时会显著提高血液乙醛水平。这些动物的线粒体 AIDH 活性相应降低至对照动物的 20% 或更低。与微粒体孵育时未将线粒体 AlDH 活性抑制到这种程度的化合物，不会产生显著水平的丙炔醛。因此，对于这一系列化合物，代谢去炔丙基化是体内 AIDH 抑制活性的必要条件。
