antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2025-70-9-10-62-76SXJVHWantibiotics-1296Research ArticleОБЗОРЫREVIEWSСтратегия создания новых антимикотиков, действующих на клеточную стенку и клеточную мембрану грибовA Strategy for the Development of New Antimycotics Acting on the Cell Wall and Cell Membrane of Fungihttps://orcid.org/0000-0001-5098-5379АвтономоваА. В.AvtonomovaA. V.

Автономова Анастасия Витальевна — к. б. н., старший научный сотрудник лаборатории биосинтеза биологически активных веществ 

Москва

Anastasia V. Avtonomova — Ph. D. in Biology, Senior Researcher at the Laboratory of Biosynthesis of Biologically Active Substances

Moscow

nomova@yandex.ruhttps://orcid.org/0000-0003-4799-1318КисильО.  В.KisilO. V.

Ольга Валерьевна Кисиль — к. х. н., ученый секретарь 

Москва

Olga V. Kisil — Ph. D. in Chemistry, Academic Secretary

Moscow

https://orcid.org/0000-0003-3898-7851ЛысенковаЛ. Н.LysenkovaL. N.

Лысенкова Людмила Николаевна — к. б. н., старший научный сотрудник лаборатории химической трансформации антибиотиков

Москва

Lyudmila Nikolaevna Lysenkova — Ph. D. in Biology, Senior Researcher at the Laboratory of Chemical Transformation of Antibiotics

Moscow

https://orcid.org/0000-0002-0391-0339КраснопольскаяЛ.  М.KrasnopolskayaL. M.

Краснопольская Лариса Михайловна — д. б. н., ведущий научный сотрудник, заведующая лабораторией биосинтеза биологически активных веществ

Москва

Larissa M. Krasnopolskaya — D. Sc. in Biology, Leading Researcher, Head of the Laboratory of Biosynthesis of Biologically Active Substances

Moscow

ФГБНУ «Научно-исследовательский институт по изысканию новых антибиотиков им. Г. Ф. Гаузе»РоссияGause Institute of New AntibioticsRussian Federation202530102025709-106276Copyright © Автономова А.В., Кисиль О. ., Лысенкова Л.Н., Краснопольская Л.М., 20262026Автономова А.В., Кисиль О. ., Лысенкова Л.Н., Краснопольская Л.М.Avtonomova A.V., Kisil O.V., Lysenkova L.N., Krasnopolskaya L.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/1296

Актуальность. Инвазивные микозы представляют растущую угрозу для здоровья, особенно для пациентов с ослабленным иммунитетом, количество которых увеличивается благодаря прогрессу в онкологии, трансплантологии и реаниматологии. Применение существующих антимикотиков ограничено их токсичностью, узким спектром действия, низкой биодоступностью и растущей резистентностью патогенов. Медленные темпы разработки новых антимикотиков по сравнению с антибактериальными препаратами усугубляют ситуацию, что делает поиск новых эффективных и безопасных препаратов чрезвычайно актуальным. Цель обзора — обобщить и систематизировать сведения о современных направлениях в разработке антимикотиков, охватывающие эволюцию подходов к «классическим» мишеням (клеточная стенка, клеточная мембрана) и стратегии, нацеленные на преодоление текущих ограничений противогрибковой терапии. Методы. Систематический анализ научной литературы и данных клинических исследований с использованием баз данных Google Scholar, eLibrary, PubMed, Wally и ClinicalTrials.gov. Основное внимание уделено публикациям последнего десятилетия и ключевым работам более раннего периода. Результаты. За последние 10 лет в клиническую практику вошли лишь 4 новых препарата. В стадии активных клинических исследований находятся 9 молекул, включая ингибиторы Gwt1, дигидро-оротатдегидрогеназы и ингаляционные триазолы. Перспективны соединения с новыми механизмами действия, например, мандимицин, нацеленный на фосфолипиды, ингибиторы отсутствующей у человека синтазы инозитол-фосфоцерамида. Заключение. Несмотря на вызовы, связанные с эукариотической природой грибов, разработка новых антимикотиков продолжается по нескольким перспективным направлениям, заключающимся в улучшении свойств представителей существующих классов и поиском принципиально новых мишеней.

Background. Invasive mycoses pose a growing health threat, especially for patients with weakened immune systems, whose number is increasing due to advances in oncology, transplantation, and intensive care. The limitations of existing antimycotics are their toxicity, narrow spectrum of action, low bioavailability, and growing resistance of pathogens. The slow pace of development of new antifungal agents compared to antibacterial ones exacerbates the situation, which makes the search for new effective and safe drugs critical. The aim of this review was to summarize and systematize information on current trends in the development of antimycotics, covering both the evolution of approaches to «classical» targets (cell wall, cell membrane) and strategies aimed at overcoming the current limitations of antifungal therapy. Methods. A systematic analysis of scientific literature and clinical research data was carried out using Google Scholar, eLibrary, PubMed, Wally, and ClinicalTrials.gov databases. The main focus was on the publications of the last decade, taking into account the key earlier studies. Results. Over the past 10 years, only 4 new drugs have entered clinical practice. There are 9 molecules in active clinical trials, including Gwt1 inhibitors, dihydroorotate dehydrogenases, and inhaled triazoles. Compounds with new mechanisms of action are of particular interest, for example, mandimycin, which targets phospholipids, inhibitors of inositol-phosphoceramide synthase, which is absent in humans. Conclusion. Despite the challenges associated with the eukaryotic nature of fungi, the development of new antimycotics continues in several promising areas focused on improving the properties of representatives of existing classes, as well as searching for fundamentally new targets.

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The authors declare that there are no conflicts of interest present.