{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T11:04:30Z","timestamp":1782471870629,"version":"3.54.5"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPERO\/SESAU-RO\/Brazilian Ministry of Health","award":["PPSUS 01\/2020, 35005.544.23035.26092020"],"award-info":[{"award-number":["PPSUS 01\/2020, 35005.544.23035.26092020"]}]},{"name":"FAPERO\/SESAU-RO\/Brazilian Ministry of Health","award":["INCT-EPIAMO, 465657\/2014-1"],"award-info":[{"award-number":["INCT-EPIAMO, 465657\/2014-1"]}]},{"name":"National Institute of Epidemiology in the Western Amazon","award":["PPSUS 01\/2020, 35005.544.23035.26092020"],"award-info":[{"award-number":["PPSUS 01\/2020, 35005.544.23035.26092020"]}]},{"name":"National Institute of Epidemiology in the Western Amazon","award":["INCT-EPIAMO, 465657\/2014-1"],"award-info":[{"award-number":["INCT-EPIAMO, 465657\/2014-1"]}]},{"name":"Excellence in Research Program of the Foundation for Scientific and Technological Development in Health of Fiocruz","award":["PPSUS 01\/2020, 35005.544.23035.26092020"],"award-info":[{"award-number":["PPSUS 01\/2020, 35005.544.23035.26092020"]}]},{"name":"Excellence in Research Program of the Foundation for Scientific and Technological Development in Health of Fiocruz","award":["INCT-EPIAMO, 465657\/2014-1"],"award-info":[{"award-number":["INCT-EPIAMO, 465657\/2014-1"]}]},{"name":"Brazilian National Council for Science and Technology","award":["PPSUS 01\/2020, 35005.544.23035.26092020"],"award-info":[{"award-number":["PPSUS 01\/2020, 35005.544.23035.26092020"]}]},{"name":"Brazilian National Council for Science and Technology","award":["INCT-EPIAMO, 465657\/2014-1"],"award-info":[{"award-number":["INCT-EPIAMO, 465657\/2014-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Capirona macrophylla is a Rubiaceae known as \u201cmulateiro\u201d. 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 Leishmania amazonensis and Plasmodium falciparum were evaluated. Methods: The extracts were analyzed by UHPLC\/HRMSn 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 Leishmania and P. falciparum, 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\u2212 spectra among the \u201cmulateiro\u201d 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 L. amazonensis with IC50 values ranging from 175.2 \u03bcg\/mL to 194.8 \u03bcg\/mL, and fraction G29 showed an IC50 of 119.8 \u03bcg\/mL against P. falciparum. Conclusions: The ethnobotanical use of \u201cmulateiro\u201d 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.<\/jats:p>","DOI":"10.3390\/metabo15030157","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:46:37Z","timestamp":1740545197000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Bioactive Metabolites of Capirona macrophylla by Metabolomic Analysis, Molecular Docking, and In Vitro Antiparasitic Assays"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5401-1758","authenticated-orcid":false,"given":"Joseph","family":"Evaristo","sequence":"first","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise de","family":"Laia","sequence":"additional","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Tavares","sequence":"additional","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esdras","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Bioinformatic and Medicinal Chemistry Laboratory, Fiocruz\/RO, Porto Velho 76812-245, Rond\u00f4nia, Brazil"},{"name":"National Institute of Epidemiology in the Western Amazon (INCT-EPIAMO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"Grisostenes","sequence":"additional","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-952X","authenticated-orcid":false,"given":"Welington","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Malaria and Leishmaniasis Bioassays Platform Laboratory, Fiocruz\/RO, Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Garcia","sequence":"additional","affiliation":[{"name":"Malaria and Leishmaniasis Bioassays Platform Laboratory, Fiocruz\/RO, Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Guterres","sequence":"additional","affiliation":[{"name":"Chemistry Department, Federal University of Rond\u00f4nia (UNIR), Rio de Janeiro City 21941-598, Rio de Janeiro State, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5507-7142","authenticated-orcid":false,"given":"F\u00e1bio","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Laboratory of Proteomics (LabProt), LADETEC, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro City 21941-598, Rio de Janeiro State, Brazil"},{"name":"Laboratory of Protein Chemistry-Proteomic Unit, Center for Research in Precision Medicine (CPMP), Carlos Chagas Filho Biophysics Institute, UFRJ, Rio de Janeiro City 21941-902, Rio de Janeiro State, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3386-0069","authenticated-orcid":false,"given":"Fernando","family":"Zanchi","sequence":"additional","affiliation":[{"name":"Bioinformatic and Medicinal Chemistry Laboratory, Fiocruz\/RO, Porto Velho 76812-245, Rond\u00f4nia, Brazil"},{"name":"National Institute of Epidemiology in the Western Amazon (INCT-EPIAMO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-8832","authenticated-orcid":false,"given":"Geisa","family":"Evaristo","sequence":"additional","affiliation":[{"name":"Center for the Study of Biomolecules Applied to Health (Cebio), Oswaldo Cruz Foundation Rond\u00f4nia Unity (Fiocruz\/RO), Porto Velho 76812-245, Rond\u00f4nia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.11646\/phytotaxa.443.1.9","article-title":"A New Revision of Capirona (Rubiaceae, Ixoroideae, Condamineeae), with a New Combination and Additional Notes on Typification of the Names Involved","volume":"443","author":"Delprete","year":"2020","journal-title":"Phytotaxa"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1590\/2175-78602005568634","article-title":"Flora Da Reserva DUCKE, Amazonas, Brasil: Rutaceae","volume":"56","author":"Taylor","year":"2005","journal-title":"Rodrigu\u00e9sia"},{"key":"ref_3","first-page":"1","article-title":"Capirona Spruce Capirona Macrophylla (Poepp)","volume":"58","author":"Cardoso","year":"2020","journal-title":"Delprete"},{"key":"ref_4","unstructured":"Pianowski, L.F., Dudycz, L.W., and Pianowski Filho, L.F. 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