Antifungal Macrocycle Antibiotic Amphotericin B—Its Present and Future. Multidisciplinary Perspective for the Use in the Medical Practice

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-02-14 DOI:10.1134/S1990750822010024

A. A. Baghirova, Kh. M. Kasumov

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Abstract—

This review is devoted to a broad analysis of the results of studies of the effect of macrocyclic antifungal polyene antibiotic amphotericin B on cell membranes. A detailed study of polyenes has shown that some of them can have not only antifungal, but also antiviral and antitumor effects. Under conditions of global pandemic fungal pathology develops especially quickly and in this case leads to invasive aspergillosis, which contributes to the complication of coronavirus infection in the lungs and even secondary infection with invasive aspergillosis. The treatment of an invasive form of bronchopulmonary aspergillosis is directly related to the immunomodulatory and immunostimulating properties of the macrocyclic polyene drug amphotericin B. The article presents experimental data on the study of the biological activity and membrane properties of amphotericin B and the effect of its chemically modified derivatives, as well as liposomal forms of amphotericin B on viral, bacterial and fungal infections. The mechanism of action of amphotericin B and its analogues is based on their interaction with cellular and lipid membranes, followed by formation of ion channels of molecular size in the membranes. The importance of these studies is that polyenes are sensitive to membranes that contain sterols of a certain structure. The analysis showed that pathogenic fungal cells containing ergosterol were 10−100 times more sensitive to polyene antibiotics than host cell membranes containing cholesterol. The high sterol selectivity of the action of polyenes opens broad prospects for the use of polyene antifungal drugs in practical medicine and pharmacology in the treatment of invasive mycoses and the prevention of atherosclerosis. In this context, it should be noted that polyene antibiotics are the main tool in the study of the biochemical mechanism of changes in the permeability of cell membranes for energy-dependent substrates. Chemical and genetic engineering transformation of the structure of polyene antibiotic molecules opens prospects for the identification and creation of new biologically active forms of the antibiotic that have a high selectivity of action in the treatment of pathogenic infections.

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抗真菌大循环抗生素两性霉素b的现状与未来。多学科视角在医学实践中的应用

摘要:本文综述了大环抗真菌多烯抗生素两性霉素B (amphotericin B)对细胞膜作用的研究结果。对多烯的详细研究表明，其中一些多烯不仅具有抗真菌作用，而且具有抗病毒和抗肿瘤作用。在全球大流行的情况下，真菌病理发展特别迅速，在这种情况下导致侵袭性曲霉病，这有助于肺部冠状病毒感染的并发症，甚至继发感染侵袭性曲霉病。侵袭性支气管肺曲霉病的治疗与大环多烯药物两性霉素B的免疫调节和免疫刺激特性直接相关。本文介绍了两性霉素B的生物活性和膜特性及其化学修饰衍生物的作用的实验数据，以及两性霉素B脂质体形式对病毒、细菌和真菌感染的作用。两性霉素B及其类似物的作用机制是基于它们与细胞和脂质膜的相互作用，然后在膜上形成分子大小的离子通道。这些研究的重要性在于，多烯对含有某种结构的固醇的膜很敏感。分析表明，含有麦角甾醇的病原真菌细胞对多烯抗生素的敏感性是含有胆固醇的宿主细胞膜的10 ~ 100倍。多烯的高甾醇选择性作用为多烯抗真菌药物在治疗侵袭性真菌病和预防动脉粥样硬化方面的应用开辟了广阔的医学和药理学应用前景。在这种情况下，应该指出的是，多烯抗生素是研究能量依赖性底物细胞膜通透性变化的生化机制的主要工具。多烯抗生素分子结构的化学和基因工程转化为鉴定和创造新的生物活性形式的抗生素开辟了前景，这些抗生素在治疗致病性感染方面具有高选择性的作用。

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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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

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0.00%

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期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.