New preparations in systemic fungal infections

Abstract

Systemic (invasive) fungal infections have been a medical and public health problem for the past 2 decades. It has been estimated that globally 1-1,2 billion people are affected by fungi with about 1,5 million deaths annually. Environmental and socio-economic factors, an increase in the number of immunocompromised patients and resistance to antifungals, as well as the limited arsenal of antifungal preparations for the treatment of invasive fungal infections urgently require the development of new classes of antifungals with advantageous pharmacokinetic, pharmacodynamic and pharmacotoxicological properties. The scope is to evaluate the literature sources regarding new strategies applied in the development and both clinical and experimental research of contemporary antifungals. Materials and methods Scientific articles from the last 5 years were selected and analysed regarding the development strategies, and experimental and clinical research of some new groups of antimycotics. Results and discussion The analysis of bibliographic sources showed a special interest in the following antifungal groups and preparations: triazoles (opelconazole); tetrazoles (oteseconazole, quileconazole); echinocandins (rezafungin); orotomides (oloropfim); nucleoside peptides (nikkomycin Z); triterpenoids (ibrexafungerp); phosphonoxoymethylenes (fosmanogepix); polyoxins (polyoxin A); macrolides (galbonolide); siderophores (VL-2397); arylamidines (ATI-2307); semi-synthetic polyenes (BSG005) etc. New groups and preparations have been shown to have new targets in fungal cells by inhibiting: beta-glucan synthase (rezafungin, ibrexafungerp); chitin-synthase (nikkomycin Z, polyoxin A); dihydroorotate dehydrogenase (holorofim); glycosylphosphatidylinositol anchored wall transfer protein 1 (fosmanogepix); 14-alpha-demethylase (oteseconazole, quileconazole); respiratory chain of mitochondria (arylamidine ATI-2307); sphingolipid synthesis (galbonolide); histone deacetylases (tricostatin A, MGCD-290); calcineurin (chromafungin); Hsp90 shock protein, etc. Simultaneously with development of new groups of antimycotic preparations, better performing medicinal forms are also being developed for amphotericin B (lipid conjugates, liposomes, emulsions, nanoparticles etc.); itraconazole (capsules dispersed on polymer matrices); terbinafine (topical solution, varnishes, etc.). Conclusions The development of new groups of antifungals was based on the in-depth study of the structural and metabolic components of fungi, which allowed them to target the cell wall, cytoplasmic membrane, mitochondria, and intracellular signalling pathways.