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Reassessing the Use of Undecanoic Acid as a Therapeutic Strategy for Treating Fungal Infections

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Abstract

Treating fungal infections is challenging and frequently requires long-term courses of antifungal drugs. Considering the limited number of existing antifungal drugs, it is crucial to evaluate the possibility of repositioning drugs with antifungal properties and to revisit older antifungals for applications in combined therapy, which could widen the range of therapeutic possibilities. Undecanoic acid is a saturated medium-chain fatty acid with known antifungal effects; however, its antifungal properties have not been extensively explored. Recent advances indicate that the toxic effect of undecanoic acid involves modulation of fungal metabolism through its effects on the expression of fungal genes that are critical for virulence. Additionally, undecanoic acid is suitable for chemical modification and might be useful in synergic therapies. This review highlights the use of undecanoic acid in antifungal treatments, reinforcing its known activity against dermatophytes. Specifically, in Trichophyton rubrum, against which the activity of undecanoic acid has been most widely studied, undecanoic acid elicits profound effects on pivotal processes in the cell wall, membrane assembly, lipid metabolism, pathogenesis, and even mRNA processing. Considering the known antifungal activities and associated mechanisms of undecanoic acid, its potential use in combination therapy, and the ability to modify the parent compound structure, undecanoic acid shows promise as a novel therapeutic against fungal infections.

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Funding

We thank the Brazilian funding agencies for the continuous support to our projects: São Paulo Research Foundation - FAPESP (proc. Nos. 2019/22596-9, 2018/11319-1, 2018/15458-6, 2015/23435-8, 2009/08411-4); National Council for Scientific and Technological Development -CNPq (proc. Nos. 305797/2017-4, and 304989/2017-7); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Finance Code 001), and Fundação de Apoio ao Ensino, Pesquisa e Assistência - FAEPA.

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  1. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, USP, Ribeirão Preto, SP, 14049-900, Brazil

    Antonio Rossi, Maíra P. Martins, Tamires A. Bitencourt, Carlos H. L. Rocha, Flaviane M. G. Rocha, João Neves-da-Rocha, Marcos E. R. Lopes, Pablo R. Sanches, Júlio C. Bortolossi & Nilce M. Martinez-Rossi

  2. Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Nalu T. A. Peres

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  1. Antonio Rossi
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All authors wrote sections of the manuscript. NM-R, MM, and AR edited the manuscript. All authors read and approved the submitted version.

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Rossi, A., Martins, M.P., Bitencourt, T.A. et al. Reassessing the Use of Undecanoic Acid as a Therapeutic Strategy for Treating Fungal Infections. Mycopathologia 186, 327–340 (2021). https://doi.org/10.1007/s11046-021-00550-4

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