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某些杂环、环状和含氮化合物对无细胞测试系统中多胺氧化脱氨的影响。

Influence of Some Heterocyclic, Cyclic, and Nitrogen-Containing Compounds on Oxidative Deamination of Polyamines in a Cell-Free Test System.

机构信息

V. A. Frolov Department of General Pathology and Pathological Physiology, Institute of Medicine, RUDN University, Moscow, Russia.

出版信息

Bull Exp Biol Med. 2024 Jul;177(3):307-312. doi: 10.1007/s10517-024-06179-9. Epub 2024 Aug 10.

Abstract

We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation - spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength.

摘要

我们研究了一些含氮杂环和环状化合物对高增殖率组织中多胺和腐胺氧化脱氨速率的影响。为此,使用来自再生大鼠肝的无细胞测试系统,测定多胺氧化降解的主要酶 - 精脒氧化酶(SMO)、多胺氧化酶(PAO)和二胺氧化酶(DAO)的比活性。化合物 2-(5-甲酰基呋喃-2-基)苯甲酸甲酯和 2,7-双-[2-(二乙氨基)乙氧基]-9H-芴-9-酮(以二盐酸盐的形式)主要对腐胺、亚精胺和精脒的氧化降解表现出激活作用,这间接表明它们具有抗增殖作用。不含氮的化合物抑制了这一过程,因此表现出潜在的致癌特性。计算了 DAO、PAO 和 SMO 的活性与 5 个拓扑指数之间的相关性:Wiener(W)、Rouvray(R)、Trinaistich 修饰的Balaban(J)、绕道(Ip)和电熵(Ie)。DAO 和 Balaban 指数(R=-0.55)之间、PAO 和绕道指数(R=0.78)之间以及 SMO 和电熵指数(R=0.53)之间存在最高的依赖性。其余的依赖性显示出不显著的相关性强度。

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