RESUMEN
The rise of antimicrobial-resistant phenotypes and the spread of the global pandemic of COVID-19 are worsening the outcomes of hospitalized patients for invasive fungal infections. Among them, candidiases are seriously worrying, especially since the currently available drug armamentarium is extremely limited. We recently reported a new class of macrocyclic amidinoureas bearing a guanidino tail as promising antifungal agents. Herein, we present the design and synthesis of a focused library of seven derivatives of macrocyclic amidinoureas, bearing a second phenyl ring fused with the core. Biological activity evaluation shows an interesting antifungal profile for some compounds, resulting to be active on a large panel of Candida spp. and C. neoformans. PAMPA experiments for representative compounds of the series revealed a low passive diffusion, suggesting a membrane-based mechanism of action or the involvement of active transport systems. Also, compounds were found not toxic at high concentrations, as assessed through MTT assays.
Asunto(s)
COVID-19 , Cryptococcus neoformans , Antifúngicos/farmacología , Pruebas de Sensibilidad Microbiana , CandidaRESUMEN
BACKGROUND: Onychomycosis (OM) accounts for about 50% of nail disorders in industrialised countries. Essential oils (EOs), aromatic natural compounds, are known for their antimicrobial activity. OBJECTIVE: The aim of this work was to evaluate the antifungal efficacy of seven EOs and a commercial MIX against 10 dermatophytes responsible for OM to select the most effective ones to be included in a preventive or curative formulation based on a green natural nail polish (GNNP). METHODS: Micro-broth dilution tests in line with EUCAST guidelines and olfactory satisfaction test were performed to select the best natural compounds previously analysed by SPME coupled with GC-MS. The same method was used to evaluate the release over time of the active compounds present in the two modified-GNNPs made by adding the best natural compound selected (the C. citratus EO) and the MIX. Furthermore, to evaluate the preventive and curative activity of modified-GNNPs, ex vivo experiments on healthy or colonised nails were performed. RESULTS AND CONCLUSIONS: Data showed that MIX-modified-GNNP had preventive activity as it inhibits the fungal growth by releasing its active ingredients for 7 days, while the OE-modified GNNP acts as a natural drug showing cytocidal activity on nails colonised by dermatophytes, but it requires two weekly applications.
Asunto(s)
Aceites Volátiles , Onicomicosis , Humanos , Onicomicosis/tratamiento farmacológico , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Polonia , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , UñasRESUMEN
The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.
Asunto(s)
Antifúngicos , Candida , Animales , Antifúngicos/química , Antifúngicos/farmacología , Biopelículas , Candida albicans , Humanos , Larva , Lipopéptidos/farmacología , Mamíferos , Pruebas de Sensibilidad MicrobianaRESUMEN
The extensive use of antibiotics has contributed to the current antibiotic resistance crisis. Livestock infections of Salmonella spp, Clostridium spp. and E. coli antimicrobial-resistant bacteria represent a public threat to human and animal health. To reduce the incidence of these zoonoses, essential oils (EOs) could be effective antibiotic alternatives. This study aims at identifying EOs safe for use, effective both in complementary therapy and in the environmental sanitization of intensive farming. Natural products were chemo-characterized by gas chromatography. Three S. Typhimurium, three C. perfringens and four E. coli strains isolated from poultry and swine farms were used to assess the antimicrobial properties of nine EOs and a modified GR-OLI (mGR-OLI). The toxicity of the most effective ones (Cinnamomum zeylanicum, Cz; Origanum vulgare, Ov) was also evaluated on porcine spermatozoa and Galleria mellonella larvae. Cz, Ov and mGR-OLI showed the strongest antimicrobial activity; their volatile components were also able to significantly inhibit the growth of tested strains. In vitro, Ov toxicity was slightly lower than Cz, while it showed no toxicity on G. mellonella larvae. In conclusion, the study confirms the importance of evaluating natural products to consolidate the idea of safe EO applications in reducing and preventing intensive livestock infections.
RESUMEN
A modern painting is characterized by multi-material bases extremely exposed to biodeteriogenic attacks. The aim of this work was to test the antifungal effectiveness of a natural, eco-friendly, and safe emulsion based on Citrus aurantium L. var. amara hydrolate and Cinnamomum zeylanicum Blume (from bark) essential oil, named "Zeylantium green emulsion" (Zege), on modern paintings. Colored unaged and aged canvas samples, performed with modern techniques (acrylic, vinylic and alkyd), were used to test in vitro both the antifungal effectiveness of Zege and its impact on the chemical-physical characteristics. Microbiological tests were performed according to the EUCAST international guidelines. pH measurements and colorimetric analysis were performed on unaged and aged canvases before and after Zege spray treatment. Finally, in situ tests were performed using the spray emulsion on canvas samples obtained from Ilaria Margutti's modern artwork, which had been colonized by molds. Microbiological tests on canvas prototypes showed a time- and dose-dependent effectiveness of the Zege spray. None of the techniques underwent relevant changes in pH. Only the acrylic colors were unaffected in the colorimetric analysis, among all colored unaged or aged canvases. Tests made with modern artwork samples confirmed the in situ antifungal effectiveness. The Zege spray showed encouraging results in regard to the use of this formulation in the restoration of modern paintings.