CHEMISTRY OF DRUG ACTION OF SOME MAO INHIBITORS

已知单胺氧化酶（MAO）抑制剂是重要的抗抑郁药， 抗高血压药。 我们的初步研究表明， N-环丙基-N-芳烷基胺是一类有效的单胺氧化酶抑制剂，具有自杀性 MAO的灭活剂。 设计了实验来验证所提出的机理 这种不可逆的失活。 这包括深入了解 MAO催化氧化单胺的化学机理。 除了 使用标记底物和抑制剂的酶促反应，非酶促模型 将采用反应。 可逆抑制剂的氧化化学 也将进行调查，以帮助了解的机制， N-环丙基-N-芳基烷基胺的失活和氧化途径 由MAO催化。 一种化合物将作为一种新的单胺氧化酶灭活剂进行试验， 设计成通过共价键连接到除黄素以外的活性位点残基上， 自杀失活机制。 此外，一类新的潜在的单胺氧化酶灭活剂 会得到考验

Monoamine oxidase (MAO) inhibitors are known to be important antidepressant and antihypertensive agents. Our initial studies indicate that N-cyclopropyl-N-arylalkyl amines, a class of potent MAO inhibitors, are suicide inactivators of MAO. Experiments are designed to confirm the mechanism proposed for this irreversible inactivation. This includes gaining insight into the chemical mechanism of oxidation of monoamines catalyzed by MAO. In addition to enzymatic reactions using labeled substrates and inhibitors, non-enzymatic model reactions will be employed. The chemistry of oxidation of reversible inhibitors also will be investigate to assist in understanding the mechanisms of inactivation of the N-cyclopropyl-N-arylakyl amines and the oxidation pathway catalyzed by MAO. A compound will be tested as a new inactivator of MAO, designed to covalently attach to an active site residue other than flavin via a suicide inactivator mechanism. Also, a new class of potential MAO inactivators will be tested.