RESUMEN
Aim: An IsCT analogue peptide (PepM3) was designed based on structural studies of wasp mastoparans and tested against Candida albicans. Its effects on fungal cell membranes and toxicity were evaluated. Materials & methods: Antifungal activity was analyzed using a microdilution susceptibility test. Toxicity was assessed using human skin keratinocytes (HaCaT) and zebrafish embryos. Results: PepM3 demonstrated activity against C. albicans and a synergistic effect with amphotericin B. The peptide presented fungicidal action with damage to the fungal cell membrane, low toxicity in HaCat cells and was nonteratogenic in zebrafish embryos. Conclusion: Evaluating structural modifications is essential for the development of new agents with potential activity against fungal pathogens and for the reduction of toxic and teratogenic effects.
Asunto(s)
Candida albicans , Pez Cebra , Animales , Humanos , Antifúngicos/toxicidad , Antifúngicos/química , Anfotericina B/farmacología , Péptidos/toxicidad , Pruebas de Sensibilidad MicrobianaRESUMEN
Aim: Octyl gallate (OG) loaded into a nanostructured lipid system (NLS) was tested for antifungal activity and in vitro and in vivo toxicity. Methods & Results: The features of NLS-OG were analyzed by dynamic light scattering and showed adequate size (132.1 nm) and homogeneity (polydispersity index = 0.200). OG was active against Paraccoccidioides spp., and NLS-OG did not affect antifungal activity. NLS-OG demonstrated reduced toxicity to lung cells and zebrafish embryos compared with OG, whereas NLS was toxic to hepatic cells. OG and NLS-OG did not show toxicity in a Galleria mellonella model at 20 mg/kg. All toxic concentrations were superior to MIC (antifungal activity). Conclusion: These results indicate good anti-Paracoccidioides activity and low toxicity of NLS-OG.
Plain language summary Drugs for the treatment of fungal diseases are limited in number and present side effects, drug interactions, risks for pregnant women and fungal resistance. The authors produced a derivative compound from plants called octyl gallate (OG) and then incorporated it into a nanoparticle lipid system (NLS) for better distribution in biological fluids. NLS-OG was tested against a fungus called Paracoccidioides, which causes lung infections. The toxicity profile of NLS-OG was also evaluated in lung and hepatic cells as well as novel animal models. NLS-OG presented good antifungal activity and low toxicity in lung cells and embryos.
Asunto(s)
Antifúngicos , Paracoccidioides , Animales , Antifúngicos/toxicidad , Ácido Gálico/análogos & derivados , Lípidos , Pez CebraRESUMEN
Aim: This study aimed to evaluate the activity of 2'-hydroxychalcone-loaded in nanoemulsion (NLS + 2'chalc), the cytotoxic effect and toxicity against Paracoccidioides brasiliensis and Paracoccidioides lutzii using a zebrafish model. Materials & methods: Preparation and physical-chemical characterization of nanoemulsion (NLS) and NLS + 2'chalc were performed. MIC and minimum fungicide concentration, cytotoxicity and toxicity were also evaluated in the Danio rerio model. Results: NLS + 2'chalc showed fungicidal activity against Paracoccidioides spp. without cytotoxicity in MRC5 and HepG2 lines. It also had high selectivity index values and no toxicity in the zebrafish model based on MIC values. Conclusion: NLS + 2'chalc is a potential new alternative treatment for paracoccidioidomycosis.
Asunto(s)
Antifúngicos/farmacología , Chalconas/farmacología , Paracoccidioides/efectos de los fármacos , Animales , Línea Celular , Chalconas/química , Emulsiones/farmacología , Fibroblastos/efectos de los fármacos , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Animales , Nanopartículas , Paracoccidioidomicosis/microbiología , Pez CebraRESUMEN
Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos/farmacología , Venenos de Avispas/farmacología , Animales , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Péptidos y Proteínas de Señalización Intercelular/efectos adversos , Péptidos y Proteínas de Señalización Intercelular/toxicidad , Queratinocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Péptidos/administración & dosificación , Péptidos/efectos adversos , Péptidos/toxicidad , Venenos de Avispas/administración & dosificación , Venenos de Avispas/efectos adversos , Venenos de Avispas/toxicidad , Pez CebraRESUMEN
AIM: Geraniol and linalool are major constituents of the essential oils of medicinal plants. MATERIALS & METHODS: Antifungal activity of geraniol and linalool were evaluated against five Candida species. The genotoxicity of these compounds was evaluated by the cytokinesis-block micronucleus test, and the embryotoxic assays use zebrafish model. RESULTS: Geraniol and linalool inhibited Candida growth, but geraniol was more effective. The geraniol at concentration of 800 µg/ml and the linalool at concentration of 125 µg/ml significantly increased chromosome damage. Geraniol was more toxic to zebrafish embryo than linalool: LC50 values were 31.3 and 193.3 µg/ml, respectively. CONCLUSION: Geraniol and linalool have anticandidal activity, but they also exert genotoxic and embryotoxic effects at the highest tested concentrations.