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Review
. 2019 Apr;11(8):869-883.
doi: 10.4155/fmc-2018-0465. Epub 2019 Apr 17.

Targeting the fungal cell wall: current therapies and implications for development of alternative antifungal agents

Sahar Hasim  1 , Jeffrey J Coleman  1
Affiliations
Review

Targeting the fungal cell wall: current therapies and implications for development of alternative antifungal agents

Sahar Hasim et al. Future Med Chem. 2019 Apr.

Abstract

Fungal infections are a worldwide problem associated with high morbidity and mortality. There are relatively few antifungal agents, and resistance has emerged within these pathogens for the newest antifungal drugs. As the fungal cell wall is critical for growth and development, it is one of the most important targets for drug development. In this review, the currently available cell wall inhibitors and suitable drug candidates for the treatment of fungal infections are explored. Future studies of the fungal cell wall and compounds that have detrimental effects on this important outer structural layer could aid in antifungal drug discovery and lead to the development of alternative cell wall inhibitors to fill gaps in clinical therapies for difficult-to-treat fungal infections.

Keywords: antifungal drug; chitin; fungal cell wall; mannoprotein; unmasking; β (1-3)-glucan.

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Conflict of interest statement

Financial & competing interests disclosure

The authors gratefully acknowledge the support of the National Institute of Allergy and Infectious Diseases (K22AI100983), and the article has been deposited to PubMed Central in accordance with NIH guidelines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Structure of the fungal cell wall and overview of compounds that target components.
The fungal cell wall is composed of layers of chitin and glucan with an outer layer of mannoproteins and other proteins linked by a glycosylphosphatidylinositol anchor to the cell wall (A). An overview of antifungal agents that either directly target an element of the cell wall or impede their biosynthesis (B).
<b>Figure 2.</b>
Figure 2.. Echinocandins, β (1-3)-glucan synthase inhibitors.
Caspofungin, micafungin, and anidulafungin are inhibitors of fungal β (1-3)-glucan synthesis and are approved by the US FDA.
<b>Figure 3.</b>
Figure 3.. Chitin synthase inhibitors.
Nikkomycins, polyoxin, and plagiochin are chitin synthase inhibitors and are structurally similar to UDP-N-acetylglucosamine. Their inhibitory activity derive from their ability to bind with a high affinity to the catalytic site of chitin synthases.
<b>Figure 4.</b>
Figure 4.. Structure of antifungal agents in various stages of clinical development.
Illustration of chemical structures of rezafungin (CD101), ibrexafungerp (SCY-078), E1210, pradimicin A, and poacic acid.
See this image and copyright information in PMC

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