Abstract
Given the increased antimicrobial resistance, global effort is currently focused on the identification of novel compounds, both of natural and chemical origin. The present study reports on the antifungal potential of 1-(1H-indol-3-yl) derivatives, previously known as tyrosinase inhibitors. The effect of seven compounds (indicated as 3a–g) was determined against Candida albicans ATCC 10531, three clinical isolates of Candida albicans, two clinical isolates of Candida glabrata, two clinical isolates of Candida parapsilosis and Aspergillus niger ATCC 16404. The effect of these derivatives on tyrosinase enzymatic activity was also evaluated. Results showed a fungicidal activity of compounds 3b, 3c and 3e against all tested strains at concentrations ranging between 0.250 and 1 mg/mL. Furthermore, the association between 3c and fluconazole and between 3b and caspofungin showed a trend of indifference tending toward synergism. Compound 3c was also able to inhibit microbial tyrosinase up to ~28% at the concentration of 0.250 mg/mL. These data could help provide novel therapeutics for topical use to treat fungal infections and increase the potential effectiveness of the association between novel compounds and commercial antifungals in order to combat drug resistance.
Highlights
The current therapeutic drugs for Candida spp. infections are limited to five main classes of compounds, namely, polyenes, allylamines, azoles, fluoropyrimidines, and echinocandins, with amphotericin B, terbinafine, fluconazole, 5-fluorocytosine, and caspofungin as principal representatives [1]
The cell wall represents the main target for echinocandins and nikkomycins, whereas polyenes target the membrane phospholipid bilayer; azoles, allylamines and phenyl-morphololines block the synthesis of sterol, soldarin and flucytosine target the protein synthesis and nucleic acid synthesis, respectively, whereas griseofulvin acts on the microtubule assembly
1,2,4-triazole, 1,3,4-thiadiazole and carbothioamide was evaluated against bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and the yeasts Candida albicans and Candida krusei: all compounds showed antimicrobial activity, with minimum inhibitory concentration (MIC) values of 3.125–50 μg/mL [25]
Summary
The current therapeutic drugs for Candida spp. infections are limited to five main classes of compounds, namely, polyenes, allylamines, azoles, fluoropyrimidines, and echinocandins, with amphotericin B, terbinafine, fluconazole, 5-fluorocytosine, and caspofungin as principal representatives [1]. The cell wall represents the main target for echinocandins and nikkomycins, whereas polyenes target the membrane phospholipid bilayer; azoles, allylamines and phenyl-morphololines block the synthesis of sterol, soldarin and flucytosine target the protein synthesis and nucleic acid synthesis, respectively, whereas griseofulvin acts on the microtubule assembly. Given the increased incidence of Candida spp. community-based and hospital-acquired infections [2], more effort has recently focused on the identification of novel therapeutics. Candida spp. are responsible for mucosal infections, including thrush and vaginitis, which could lead to invasive candidiasis in immunocompromised patients, especially with new species becoming multi-drug resistant [3]. C. albicans could cause cerebritis and a mild memory impairment [4]
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