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- Title
Anti- Candida albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART.
- Authors
Silva, Anderson França da; Farias, Josivan Regis; Franco, Danielle Cristine Gomes; Galiza, Andrea Araruna; Motta, Elizangela Pestana; Oliveira, Aluísio da Silva; Vasconcelos, Cleydlenne Costa; Cartágenes, Maria do Socorro de Sousa; Rocha, Claudia Quintino da; Silva, Mayara Cristina Pinto da; Lopes, Alberto Jorge Oliveira; Nascimento, Flavia Raquel Fernandes do; Monteiro, Cristina Andrade; Guerra, Rosane Nassar Meireles
- Abstract
Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of −10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives.
- Subjects
CANDIDA albicans; METABOLITES; ECHINOCANDINS; TENEBRIO molitor; ERYTHROCYTES; ANTIFUNGAL agents; ELECTRON affinity
- Publication
Metabolites (2218-1989), 2022, Vol 12, Issue 11, p1014
- ISSN
2218-1989
- Publication type
Article
- DOI
10.3390/metabo12111014