Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART
<i>Candida albicans</i> 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 dur...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/11/1014 |
| _version_ | 1797467333011177472 |
|---|---|
| author | Anderson França da Silva Josivan Regis Farias Danielle Cristine Gomes Franco Andrea Araruna Galiza Elizangela Pestana Motta Aluísio da Silva Oliveira Cleydlenne Costa Vasconcelos Maria do Socorro de Sousa Cartágenes Claudia Quintino da Rocha Mayara Cristina Pinto da Silva Alberto Jorge Oliveira Lopes Flavia Raquel Fernandes do Nascimento Cristina Andrade Monteiro Rosane Nassar Meireles Guerra |
| author_facet | Anderson França da Silva Josivan Regis Farias Danielle Cristine Gomes Franco Andrea Araruna Galiza Elizangela Pestana Motta Aluísio da Silva Oliveira Cleydlenne Costa Vasconcelos Maria do Socorro de Sousa Cartágenes Claudia Quintino da Rocha Mayara Cristina Pinto da Silva Alberto Jorge Oliveira Lopes Flavia Raquel Fernandes do Nascimento Cristina Andrade Monteiro Rosane Nassar Meireles Guerra |
| author_sort | Anderson França da Silva |
| collection | DOAJ |
| description | <i>Candida albicans</i> 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 <i>Tenebrio molitor</i> as an alternative in vivo model of infection caused by <i>C. albicans</i>. 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-<i>Candida albicans</i> 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 <i>T. molitor</i> were used as an alternative in vivo model of <i>C. albicans</i> 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-<i>Candida albicans</i> activity and is a potential candidate for the development of new therapeutic alternatives. |
| first_indexed | 2024-03-09T18:51:06Z |
| format | Article |
| id | doaj.art-a5b197dcabf84ef2a3e0996f81c38dab |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T18:51:06Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-a5b197dcabf84ef2a3e0996f81c38dab2023-11-24T05:49:39ZengMDPI AGMetabolites2218-19892022-10-011211101410.3390/metabo12111014Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MARTAnderson França da Silva0Josivan Regis Farias1Danielle Cristine Gomes Franco2Andrea Araruna Galiza3Elizangela Pestana Motta4Aluísio da Silva Oliveira5Cleydlenne Costa Vasconcelos6Maria do Socorro de Sousa Cartágenes7Claudia Quintino da Rocha8Mayara Cristina Pinto da Silva9Alberto Jorge Oliveira Lopes10Flavia Raquel Fernandes do Nascimento11Cristina Andrade Monteiro12Rosane Nassar Meireles Guerra13Laboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilProgram in Biotechnology-RENORBIO, Federal University of Maranhão, São Luís 65080-805, BrazilProgram in Health Sciences, Federal University of Maranhão, São Luís 65080-805, BrazilDepartment of Chemistry, Federal University of Maranhão, São Luís 65080-805, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilFederal Institute of Science Education and Technology of Maranhão-Campus Santa Inês, Santa Inês 65300-000, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, BrazilDepartment of Biology, Federal Institute of Science Education and Technology of Maranhão, São Luís 65030-005, BrazilLaboratory of Immunophysiolgy, Federal University of Maranhão, São Luís 65080-805, Brazil<i>Candida albicans</i> 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 <i>Tenebrio molitor</i> as an alternative in vivo model of infection caused by <i>C. albicans</i>. 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-<i>Candida albicans</i> 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 <i>T. molitor</i> were used as an alternative in vivo model of <i>C. albicans</i> 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-<i>Candida albicans</i> activity and is a potential candidate for the development of new therapeutic alternatives.https://www.mdpi.com/2218-1989/12/11/1014<i>Candida albicans</i>ononinmolecular docking<i>Tenebrio molitor</i><i>Platonia insignis</i>antifungal |
| spellingShingle | Anderson França da Silva Josivan Regis Farias Danielle Cristine Gomes Franco Andrea Araruna Galiza Elizangela Pestana Motta Aluísio da Silva Oliveira Cleydlenne Costa Vasconcelos Maria do Socorro de Sousa Cartágenes Claudia Quintino da Rocha Mayara Cristina Pinto da Silva Alberto Jorge Oliveira Lopes Flavia Raquel Fernandes do Nascimento Cristina Andrade Monteiro Rosane Nassar Meireles Guerra Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART Metabolites <i>Candida albicans</i> ononin molecular docking <i>Tenebrio molitor</i> <i>Platonia insignis</i> antifungal |
| title | Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART |
| title_full | Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART |
| title_fullStr | Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART |
| title_full_unstemmed | Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART |
| title_short | Anti-<i>Candida albicans</i> Activity of Ononin and Other Secondary Metabolites from <i>Platonia Insignis</i> MART |
| title_sort | anti i candida albicans i activity of ononin and other secondary metabolites from i platonia insignis i mart |
| topic | <i>Candida albicans</i> ononin molecular docking <i>Tenebrio molitor</i> <i>Platonia insignis</i> antifungal |
| url | https://www.mdpi.com/2218-1989/12/11/1014 |
| work_keys_str_mv | AT andersonfrancadasilva antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT josivanregisfarias antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT daniellecristinegomesfranco antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT andreaararunagaliza antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT elizangelapestanamotta antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT aluisiodasilvaoliveira antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT cleydlennecostavasconcelos antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT mariadosocorrodesousacartagenes antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT claudiaquintinodarocha antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT mayaracristinapintodasilva antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT albertojorgeoliveiralopes antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT flaviaraquelfernandesdonascimento antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT cristinaandrademonteiro antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart AT rosanenassarmeirelesguerra antiicandidaalbicansiactivityofononinandothersecondarymetabolitesfromiplatoniainsignisimart |