title: Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests.
abstract: This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 μg/mL) and Cryptococcus spp. (3-5 μg/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane.
authors.forename: Maria do Perpetuo Socorro Borges Carriço
authors.initials: Mdo P
authors.lastname: Ferreira
authors.forename: Mariana Filomena do Carmo
authors.initials: MF
authors.lastname: Cardoso
authors.forename: Fernando de Carvalho
authors.initials: Fde C
authors.lastname: da Silva
authors.forename: Vitor Francisco
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Emerson Silva
authors.initials: ES
authors.lastname: Lima
authors.affiliation: Instituto Nacional de Pesquisa,da Amazônia, Laboratório de Micologia, Manaus, AM, Brazil. joao.souza@inpa.gov.br.
authors.forename: João Vicente Braga
authors.initials: JV
authors.lastname: Souza
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000382:microbiology; D009285:Naphthoquinones / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D009285:Naphthoquinones