{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:37Z","timestamp":1787029057519,"version":"build-2736575974"},"reference-count":75,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vicerrector\u00eda de Investigaciones at Universidad Militar Nueva Granada","award":["INV-CIAS-2536, 2018"],"award-info":[{"award-number":["INV-CIAS-2536, 2018"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["309648\/2019-0, and 431254\/2018-4, 308590\/2017-1, 421254\/2018-1 and 306798\/2020-4."],"award-info":[{"award-number":["309648\/2019-0, and 431254\/2018-4, 308590\/2017-1, 421254\/2018-1 and 306798\/2020-4."]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The current treatments against Leishmania parasites present high toxicity and multiple side effects, which makes the control and elimination of leishmaniasis challenging. Natural products constitute an interesting and diverse chemical space for the identification of new antileishmanial drugs. To identify new drug options, an in-house database of 360 kauranes (tetracyclic diterpenes) was generated, and a combined ligand- and structure-based virtual screening (VS) approach was performed to select potential inhibitors of Leishmania major (Lm) pteridine reductase I (PTR1). The best-ranked kauranes were employed to verify the validity of the VS approach through LmPTR1 enzyme inhibition assay. The half-maximal inhibitory concentration (IC50) values of selected bioactive compounds were examined using the random forest (RF) model (i.e., 2\u03b2-hydroxy-menth-6-en-5\u03b2-yl ent-kaurenoate (135) and 3\u03b1-cinnamoyloxy-ent-kaur-16-en-19-oic acid (302)) were below 10 \u03bcM. A compound similar to 302, 3\u03b1-p-coumaroyloxy-ent-kaur-16-en-19-oic acid (302a), was also synthesized and showed the highest activity against LmPTR1. Finally, molecular docking calculations and molecular dynamics simulations were performed for the VS-selected, most-active kauranes within the active sites of PTR1 hybrid models, generated from three Leishmania species that are known to cause cutaneous leishmaniasis in the new world (i.e., L. braziliensis, L. panamensis, and L. amazonensis) to explore the targeting potential of these kauranes to other species-dependent variants of this enzyme.<\/jats:p>","DOI":"10.3390\/molecules26113076","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:01:20Z","timestamp":1621814480000},"page":"3076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Identification of Kaurane-Type Diterpenes as Inhibitors of Leishmania Pteridine Reductase I"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6220-9091","authenticated-orcid":false,"given":"Chonny","family":"Herrera-Acevedo","sequence":"first","affiliation":[{"name":"Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"},{"name":"Bioorganic Chemistry Laboratory, Facultad de Ciencias B\u00e1sicas y Aplicadas, Universidad Militar Nueva Granada, Cajic\u00e1 250247, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-8007","authenticated-orcid":false,"given":"Areli","family":"Flores-Gaspar","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias B\u00e1sicas y Aplicadas, Universidad Militar Nueva Granada, Cajic\u00e1 250247, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-4107","authenticated-orcid":false,"given":"Luciana","family":"Scotti","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-833X","authenticated-orcid":false,"given":"Francisco Jaime Bezerra","family":"Mendon\u00e7a-Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Synthesis and Drug Delivery, State University of Para\u00edba, Jo\u00e3o Pessoa 58071-160, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-8057","authenticated-orcid":false,"given":"Marcus Tullius","family":"Scotti","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-9749","authenticated-orcid":false,"given":"Ericsson","family":"Coy-Barrera","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Facultad de Ciencias B\u00e1sicas y Aplicadas, Universidad Militar Nueva Granada, Cajic\u00e1 250247, Colombia"},{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias B\u00e1sicas y Aplicadas, Universidad Militar Nueva Granada, Cajic\u00e1 250247, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","first-page":"142","article-title":"Neglected tropical diseases: Diagnosis, clinical management, treatment and control","volume":"22","author":"Utzinger","year":"2012","journal-title":"Swiss Med. 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