匹吲哚类似物对单胺氧化酶的抑制作用：3D-QSAR和CoMFA分析。

Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR and CoMFA analysis.

作者信息

Medvedev A E, Veselovsky A V, Shvedov V I, Tikhonova O V, Moskvitina T A, Fedotova O A, Axenova L N, Kamyshanskaya N S, Kirkel A Z, Ivanov A S

机构信息

Laboratory of Biochemistry, Russian Academy of Medical Sciences, Moscow, Russia.

出版信息

J Chem Inf Comput Sci. 1998 Nov-Dec;38(6):1137-44. doi: 10.1021/ci9802068.

DOI:10.1021/ci9802068

PMID:9845968

Abstract

A series of pyrazinocarbazoles, analogues of short acting antidepressant pirlindole (2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride), were tested as inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B). Rigid analogues exhibited potent and selective inhibition of MAO-A and have size limits (X:Y:Z) of 13.0 x 7.0 x 4.4 A. Besides MAO-A inhibition flexible analogues also demonstrated potent inhibition of MAO-B and in contrast to rigid analogues their inhibitory activity did not show the dependence on these sizes. The qualitative information (steric and electrostatic coefficients) from the 3D-QSAR with CoMFA models for MAO-A and -B are different, and this information can be used to determine the structural features influencing inhibitor selectivity.

摘要

一系列吡嗪咔唑类化合物，即短效抗抑郁药匹克隆朵（2,3,3a,4,5,6-六氢-8-甲基-1H-吡嗪并[3,2,1-j,k]咔唑盐酸盐）的类似物，被作为单胺氧化酶A（MAO-A）和B（MAO-B）的抑制剂进行了测试。刚性类似物对MAO-A表现出强效且选择性的抑制作用，其尺寸限制（X:Y:Z）为13.0×7.0×4.4埃。除了抑制MAO-A外，柔性类似物还对MAO-B表现出强效抑制作用，与刚性类似物不同的是，它们对MAO-B抑制活性不依赖于这些尺寸。来自MAO-A和-B的CoMFA模型的3D-QSAR的定性信息（空间和静电系数）不同，并且该信息可用于确定影响抑制剂选择性的结构特征。