{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:29:05Z","timestamp":1785511745584,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Competition for Research Regular Projects, year 2023","award":["LPR23-11"],"award-info":[{"award-number":["LPR23-11"]}]},{"DOI":"10.13039\/100031605","name":"Universidad Tecnol\u00f3gica Metropolitana","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031605","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Neglected tropical diseases (NTDs) caused by protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Leishmania spp., and Plasmodium falciparum remain a global health challenge due to limited therapies and increasing drug resistance. Natural products provide diverse scaffolds for antiparasitic drug discovery. This study aimed to investigate the multitarget inhibitory potential of alkaloids isolated from Croton linearis Jacq. against validated protozoan enzymes. Methods: Eighteen alkaloids were virtually screened against 17 molecular targets relevant to protozoan parasites. Protein\u2013ligand docking simulations were performed using crystallographic structures of enzymes, including Cyp51, DHFR-TS, PTR1, AD-kinase, and DHODH. Predicted interactions were analyzed to identify hydrogen bonds, hydrophobic contacts, and \u03c0\u2013\u03c0 stacking with key residues in the active sites. Results: Several alkaloids exhibited high binding affinities, in some cases surpassing co-crystallized ligands. Reticuline, norsalutaridine, laudanosine, and jacularine consistently showed the strongest activity, with docking scores ranging from \u22128.0 to \u22129.3 kcal\/mol across multiple targets. Notably, norsalutaridine displayed the highest predicted affinity for L. infantum Cyp51, while reticuline showed strong binding to T. cruzi DHFR-TS and L. major PTR1. Conclusions: The study highlights the potential of C. linearis alkaloids as multitarget inhibitors against protozoan parasites. These compounds represent promising lead candidates for the development of antiparasitic agents, while emphasizing the value of natural product scaffolds for neglected disease drug discovery. The findings also support the future exploration of semisynthetic derivatives to optimize activity and selectivity.<\/jats:p>","DOI":"10.3390\/ph18111715","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:25:27Z","timestamp":1762925127000},"page":"1715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protozoan Neglected Tropical Diseases (NTDs) Target Inhibition of Alkaloids from Croton linearis Jacq Leaves: A Molecular Docking and ADMET Approach"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8877-1592","authenticated-orcid":false,"given":"Julio A.","family":"Rojas-Vargas","sequence":"first","affiliation":[{"name":"Doctorado en Inform\u00e1tica Aplicada a Salud y Medio Ambiente, Universidad Tecnol\u00f3gica Metropolitana, Ignacio Valdivieso 2409, San Joaqu\u00edn, Santiago 8940577, Chile"},{"name":"Departament of Chemistry, Exact and Natural Science Faculty, Universidad de Oriente, Santiago de Cuba 90500, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-3417","authenticated-orcid":false,"given":"Jes\u00fas","family":"Garc\u00eda-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovsk\u00e9ho 1203, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3609-4451","authenticated-orcid":false,"given":"Julio C\u00e9sar","family":"Escalona-Arranz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Sciences, Universidad Cat\u00f3lica del Norte, Angamos 0610, Antofagasta 124 0000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0697-5242","authenticated-orcid":false,"given":"Jakub","family":"Chlebek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovsk\u00e9ho 1203, 500 05 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-809X","authenticated-orcid":false,"given":"Lianet","family":"Monzote","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Tropical Medicine \u201cPedro Kour\u00ed\u201d, Marianao 13, La Habana 10400, Cuba"},{"name":"Research Network Natural Products Against Neglected Diseases (ResNetNPND), 48149 Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-0528","authenticated-orcid":false,"given":"William N.","family":"Setzer","sequence":"additional","affiliation":[{"name":"Research Network Natural Products Against Neglected Diseases (ResNetNPND), 48149 Munster, Germany"},{"name":"Aromatic Plant Research Center, 230 N 1200 E, Suite 100, Lehi, UT 84043, USA"},{"name":"Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0896-9484","authenticated-orcid":false,"given":"Juan A.","family":"Castillo-Garit","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Investigaci\u00f3n y Desarrollo Tecnol\u00f3gico (IDT), Universidad Tecnol\u00f3gica Metropolitana, Ignacio Valdivieso 2409, San Joaqu\u00edn, Santiago 8940577, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). 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