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In this context, the search for new treatment alternatives is very relevant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Analyse chemical compounds for antifungal potential against dermatomycosis fungi.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antifungal activity of 121 compounds, intermediates or derivatives of 1,3\u2010bis(aryloxy)propane substituted at C\u20102 (111 compounds) and isothiouronium derivatives (10 compounds) was investigated through susceptibility tests, mechanism of action, toxicity and hydrogel incorporation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The compound 1,3\u2010bis(3,4\u2010dichlorophenoxy)propan\u20102\u2010aminium chloride (<jats:bold>2j<\/jats:bold>) was the most active fungicide against dermatophytes and <jats:italic>Candida<\/jats:italic> spp., at very low concentrations (0.39\u20103.12\u00a0\u00b5g\/mL), including action on resistant and multidrug\u2010resistant clinical strains. Compound <jats:bold>2j<\/jats:bold> has presented a promising toxicity profile, showing selectivity index &gt;10, relative to human lymphocytes. The compound was classified as non\u2010irritant by the HET\u2010CAM test and did not cause histopathological alterations in pig ear skin, thus presenting an excellent perspective for topical application. <jats:bold>2j<\/jats:bold> targets the fungal cell wall, which was confirmed by scanning electron microscopy, which also indicated the additional ability of <jats:bold>2j<\/jats:bold> to inhibit the <jats:italic>Candida albicans<\/jats:italic> pseudohyphae formation and biofilm of <jats:italic>Microsporum canis<\/jats:italic>. Compound <jats:bold>2j<\/jats:bold> was incorporated in a hydrogel with bioadhesive potential. The results of the human skin permeation showed that <jats:bold>2j<\/jats:bold> remained significantly in the epidermis, ideally for the dermatomycosis treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Therefore, the compound <jats:bold>2j<\/jats:bold> demonstrated the potential for antifungal drug development, with a action mechanism elucidated and already applied in a semisolid formulation as a new therapeutic option for fungal skin infections.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13027","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T07:40:08Z","timestamp":1572248408000},"page":"197-211","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3\u2010bis(3,4\u2010dichlorophenoxy)propan\u20102\u2010aminium 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