Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays
<i>Capirona macrophylla</i> is a Rubiaceae known as “mulateiro”. Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria. Objectives: The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in s...
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| author | Joseph Evaristo Elise de Laia Bruna Tavares Esdras Mendonça Larissa Grisostenes Caroline Rodrigues Welington do Nascimento Carolina Garcia Sheila Guterres Fábio Nogueira Fernando Zanchi Geisa Evaristo |
| author_facet | Joseph Evaristo Elise de Laia Bruna Tavares Esdras Mendonça Larissa Grisostenes Caroline Rodrigues Welington do Nascimento Carolina Garcia Sheila Guterres Fábio Nogueira Fernando Zanchi Geisa Evaristo |
| author_sort | Joseph Evaristo |
| collection | DOAJ |
| description | <i>Capirona macrophylla</i> is a Rubiaceae known as “mulateiro”. Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria. Objectives: The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in silico docking and in vitro cellular efficacy against <i>Leishmania amazonensis</i> and <i>Plasmodium falciparum</i> were evaluated. Methods: The extracts were analyzed by UHPLC/HRMS<sup>n</sup> using untargeted metabolomics approach with MSDial, MSFinder, and GNPS software for metabolite identification and spectra clustering. The most abundant metabolites underwent molecular docking using AutoDock via PyRx, targeting the dihydroorotate dehydrogenase from <i>Leishmania</i> and <i>P. falciparum</i>, and evaluated through molecular dynamics simulations using Gromacs. In vitro biological assays were conducted on 60 HPLC-fractions against these parasites. Results: Metabolomics analysis identified 5100 metabolites in ESI+ and 2839 in ESI− spectra among the “mulateiro” samples. GNPS clustering highlighted large clusters of quercetin and chlorogenic acid groups. The most abundant metabolites were isofraxidin, scopoletin, 5(S)-5-carboxystrictosidine, loliolide, quercetin, quinic acid, caffeoylquinic acid (and isomers), chlorogenic acid, neochlorogenic acid, tryptophan, N-acetyltryptophan, epicatechin, procyanidin, and kaempferol-3-O-robinoside-7-O-rhamnoside. Molecular docking pointed to 3,4-dicaffeoylquinic acid and kaempferol as promising inhibitors. The in vitro assays yielded four active HPLC-fractions against <i>L. amazonensis</i> with IC50 values ranging from 175.2 μg/mL to 194.8 μg/mL, and fraction G29 showed an IC50 of 119.8 μg/mL against <i>P. falciparum</i>. Conclusions: The ethnobotanical use of “mulateiro” wood bark tea as an antimalarial and antileishmanial agent was confirmed through in vitro assays. We speculate that these activities are attributed to linoleic acids and quinic acids. |
| format | Article |
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| institution | DOAJ |
| issn | 2218-1989 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-e6f5f01ace464e8496c99c73354277042025-08-20T02:42:26ZengMDPI AGMetabolites2218-19892025-02-0115315710.3390/metabo15030157Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic AssaysJoseph Evaristo0Elise de Laia1Bruna Tavares2Esdras Mendonça3Larissa Grisostenes4Caroline Rodrigues5Welington do Nascimento6Carolina Garcia7Sheila Guterres8Fábio Nogueira9Fernando Zanchi10Geisa Evaristo11Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, BrazilCenter for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, BrazilCenter for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, BrazilBioinformatic and Medicinal Chemistry Laboratory, Fiocruz/RO, Porto Velho 76812-245, Rondônia, BrazilCenter for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, BrazilCenter for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, BrazilMalaria and Leishmaniasis Bioassays Platform Laboratory, Fiocruz/RO, Porto Velho 76812-245, Rondônia, BrazilMalaria and Leishmaniasis Bioassays Platform Laboratory, Fiocruz/RO, Porto Velho 76812-245, Rondônia, BrazilChemistry Department, Federal University of Rondônia (UNIR), Rio de Janeiro City 21941-598, Rio de Janeiro State, BrazilLaboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro City 21941-598, Rio de Janeiro State, BrazilBioinformatic and Medicinal Chemistry Laboratory, Fiocruz/RO, Porto Velho 76812-245, Rondônia, BrazilCenter for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rondônia Unity (Fiocruz/RO), Porto Velho 76812-245, Rondônia, Brazil<i>Capirona macrophylla</i> is a Rubiaceae known as “mulateiro”. Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria. Objectives: The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in silico docking and in vitro cellular efficacy against <i>Leishmania amazonensis</i> and <i>Plasmodium falciparum</i> were evaluated. Methods: The extracts were analyzed by UHPLC/HRMS<sup>n</sup> using untargeted metabolomics approach with MSDial, MSFinder, and GNPS software for metabolite identification and spectra clustering. The most abundant metabolites underwent molecular docking using AutoDock via PyRx, targeting the dihydroorotate dehydrogenase from <i>Leishmania</i> and <i>P. falciparum</i>, and evaluated through molecular dynamics simulations using Gromacs. In vitro biological assays were conducted on 60 HPLC-fractions against these parasites. Results: Metabolomics analysis identified 5100 metabolites in ESI+ and 2839 in ESI− spectra among the “mulateiro” samples. GNPS clustering highlighted large clusters of quercetin and chlorogenic acid groups. The most abundant metabolites were isofraxidin, scopoletin, 5(S)-5-carboxystrictosidine, loliolide, quercetin, quinic acid, caffeoylquinic acid (and isomers), chlorogenic acid, neochlorogenic acid, tryptophan, N-acetyltryptophan, epicatechin, procyanidin, and kaempferol-3-O-robinoside-7-O-rhamnoside. Molecular docking pointed to 3,4-dicaffeoylquinic acid and kaempferol as promising inhibitors. The in vitro assays yielded four active HPLC-fractions against <i>L. amazonensis</i> with IC50 values ranging from 175.2 μg/mL to 194.8 μg/mL, and fraction G29 showed an IC50 of 119.8 μg/mL against <i>P. falciparum</i>. Conclusions: The ethnobotanical use of “mulateiro” wood bark tea as an antimalarial and antileishmanial agent was confirmed through in vitro assays. We speculate that these activities are attributed to linoleic acids and quinic acids.https://www.mdpi.com/2218-1989/15/3/157mulateirotropical diseasesUHPLC/HRMS<sup>n</sup>GNPSin silico assay |
| spellingShingle | Joseph Evaristo Elise de Laia Bruna Tavares Esdras Mendonça Larissa Grisostenes Caroline Rodrigues Welington do Nascimento Carolina Garcia Sheila Guterres Fábio Nogueira Fernando Zanchi Geisa Evaristo Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays Metabolites mulateiro tropical diseases UHPLC/HRMS<sup>n</sup> GNPS in silico assay |
| title | Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays |
| title_full | Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays |
| title_fullStr | Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays |
| title_full_unstemmed | Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays |
| title_short | Identification of Bioactive Metabolites of <i>Capirona macrophylla</i> by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays |
| title_sort | identification of bioactive metabolites of i capirona macrophylla i by metabolomic analysis molecular docking and in vitro antiparasitic assays |
| topic | mulateiro tropical diseases UHPLC/HRMS<sup>n</sup> GNPS in silico assay |
| url | https://www.mdpi.com/2218-1989/15/3/157 |
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