Abstract
Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.
Highlights
Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia; Abstract: Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden
The most pronounced antibiofilm activity at minimal inhibitory concentrations (MIC) was observed for isoquercitrin (76% inhibition) while both apigetrin and isoquercitrin applied in MIC/2 could prevent biofilm formation for more than 60% [56]
The fungal cell wall has a different structure in relation to human cells and this unique structure is an appealing target for the development of antifungal drugs [132]
Summary
Fungi are eukaryotic unicellular or multicellular organisms. They have a specific cell wall structure and cytoplasmic membrane made of sterols, primarily ergosterol. It is estimated that fungal infections, primarily the ones associated with Candida, Cryptococcus and Aspergillus species, kill more than one million people each year. These underestimated diseases are challenging to eradicate, and the linked mortality is very high even despite the existence of antifungal treatments [2]. Deep/invasive—fungi are localized and multiply in deep tissues and organs (lungs, liver, spleen, bones, brain, heart, and blood). These infections have a complex clinical course, poor prognosis, and are difficult to diagnose.
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