BIOMIMETIC APPROACHES TO STUDY OF PROPERTIES OF MEDICINAL SUBSTANCES

N. Melnikova, O. Solovyova, Evgeni N. Evgeni N. Kochetkov
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引用次数: 2

Abstract

The review is devoted to an assessment of the current level of use of biomimetic approaches to the study of the properties of known drugs and the development of new drugs. In this review, we consider the main biological functions of superoxide dismutase, namely the catalytic decomposition of toxic superoxide anion of oxygen to the molecular form of oxygen and protection against induced apoptosis. The biomimetic enzymes-Mn- and TEMPO-containing equivalents of superoxide dismutase SOD with antitumor and antioxidant activity were discussed more detail. The relationship between the properties and activity of SOD mimetics with their structure among them the nature of the anion and ligands, the coordination number, the geometry of the presence of conjugated bonds, and other parameters of the molecules. The study of the properties of Mn-SOD mimetics makes it possible to develop a new class of drugs successfully tested by in vivo and in vitro experiments and which are at the stages of clinical trials. Stable TEMPO radicals containing compounds are able to perform SOD functions, exhibiting antioxidant activity in relation not only to superoxide-anion, but also to peroxynitrile, and moreover to act as a spin label. The biomimetic membrane systems (monolayers, planar lipid bilayers, liposomes and other nano-sized objects) are discussed too for studying properties in in vitro experiments and for delivering potent and medicinal substances. The biomimetic approach combination allows to create the new promising drugs, including those based on SOD mimetics, and to develop the synthetic analogues of biologically active substances and methods of their delivery. The advantages of such dosage forms are lower toxicity of the preparations, lack of immunogenicity and a decrease in the dose of potent drugs.
药用物质性质研究的仿生方法
该综述致力于评估目前使用仿生方法来研究已知药物的性质和开发新药的水平。本文综述了超氧化物歧化酶的主要生物学功能,即催化氧的有毒超氧阴离子分解为氧的分子形式和保护诱导细胞凋亡。更详细地讨论了具有抗肿瘤和抗氧化活性的超氧化物歧化酶的mn -和tempo -等价物仿生酶。SOD模拟物的性质和活性与其结构之间的关系,其中阴离子和配体的性质、配位数、共轭键存在的几何形状以及分子的其他参数。对锰超氧化物歧化酶(Mn-SOD)模拟物性质的研究,使开发出一类通过体内和体外实验成功验证并处于临床试验阶段的新型药物成为可能。含有稳定TEMPO自由基的化合物能够执行SOD功能,不仅对超氧阴离子具有抗氧化活性,而且对过氧腈也具有抗氧化活性,而且还可以作为自旋标签。还讨论了仿生膜系统(单层、平面脂质双层、脂质体和其他纳米级物体)在体外实验中的性能研究和有效药物的输送。仿生方法的结合允许创造新的有前途的药物,包括那些基于SOD模拟物的药物,并开发生物活性物质的合成类似物及其递送方法。这种剂型的优点是制剂毒性较低,缺乏免疫原性,强效药物的剂量减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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