Modern trends in the development of antifungal agents

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Abstract

Mycoses pose an increasing threat to public health, resulting in millions of invasive infections and a high mortality rate each year. The limited arsenal of antifungal agents, their toxicity, and the rapid spread of resistance underscore the urgent need for new therapeutic strategies. This review systematizes current trends in the development of antimycotic agents intended for the treatment of invasive mycoses. The primary focus is on drugs with novel mechanisms of action targeting key structures and metabolic pathways of the fungal cell. The emphasis is on publications from the past decade; however, significant fundamental research from earlier times has also been taken into account. The search was conducted in the electronic databases eLibrary.ru, PubMed, Google Scholar, and Wally. Promising approaches include inhibition of cell wall component synthesis, disruption of cell membrane function through effects on ergosterol, phospholipids, and sphingolipids, as well as effects on intracellular targets: fungal intracellular proteins and signaling pathways, protein biosynthesis processes, and nucleic acid replication and transcription. Agents inhibiting the synthesis of major cell wall components such as β-1,3-glucan (echinocandins, ibrexafungerpY), β-1,6-glucan, chitin (nikkomycin ZY), and GPI anchors (fosmanogepixY), are reviewed. Agents acting on ergosterol (oteseconazoleY, opelconazoleY), sphingolipids (IPC-synthase inhibitorsY), and phospholipids (mandimycinY) are analyzed. Fungal kinase inhibitors, Hsp90, calcineurin, N-myristoyltransferase, elongation factor EF-2, and nucleic acids (olorofimY) are described. Several of these compounds (olorofimY, fosmanogepixY, VT-1598Y, BSG005) are currently in clinical trials. The importance of identifying selective targets and developing combination therapy to overcome resistance and improve treatment effectiveness is emphasized.

 

Y Hereafter, it means that the medicinal product is not registered in the Russian Federation.

About the authors

Anastasia V. Avtonomova

Centre for Strategic Planning and Management of Biomedical Health Risk; Gause Institute of New Antibiotics

Author for correspondence.
Email: aavtonomova@cspfmba.ru
ORCID iD: 0000-0001-5098-5379
SPIN-code: 4409-8108

Cand. Sci. (Biology)

Russian Federation, Moscow; Moscow

Olga V. Kisil

Gause Institute of New Antibiotics

Email: olvv@mail.ru
ORCID iD: 0000-0003-4799-1318
SPIN-code: 1153-8414

Cand. Sci. (Chemistry)

Russian Federation, Moscow

Angelica V. Zagainova

Centre for Strategic Planning and Management of Biomedical Health Risk

Email: azagaynova@cspfmba.ru
ORCID iD: 0000-0003-4772-9686
SPIN-code: 6642-7819

Cand. Sci. (Biology)

Russian Federation, Moscow

Valentin V. Makarov

Centre for Strategic Planning and Management of Biomedical Health Risk

Email: makarov@cspfmba.ru
ORCID iD: 0000-0001-9495-0266
SPIN-code: 7842-8808

Cand. Sci. (Biology)

Russian Federation, Moscow

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