{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T03:28:46Z","timestamp":1770089326055,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico by the program \u201cPrograma de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica\u201d","award":["IN213222"],"award-info":[{"award-number":["IN213222"]}]},{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico by the program \u201cPrograma de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica\u201d","award":["IN214225"],"award-info":[{"award-number":["IN214225"]}]},{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico by the program \u201cPrograma de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica\u201d","award":["IN215823"],"award-info":[{"award-number":["IN215823"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>The Croton genus includes a diverse group of plants with remarkable potential in natural products research, particularly due to their bioactive compounds with hypoglycemic and phytochemical significance. This study examines Croton guatemalensis Lotsy, focusing on its chemical composition and its biological efficacy as a glucose-6-phosphatase inhibitor. Phytochemical analysis led to the isolation and structural elucidation of eleven compounds (1\u201311), including three new ent\u2212clerodane diterpenes, designated crotoguatenoic acids C (9), D (10), and E (11). The absolute configurations of compounds 9\u201311 were determined by electronic circular dichroism (ECD) as (5R,8R,9R,10S)-configured ent\u2013clerodanes. High-performance liquid chromatography\u2013mass spectrometry (HPLC\u2013MS\/MS) revealed 25 peaks tentatively assigned to terpenoids, flavonoids, and alkaloids, highlighting the species\u2019 chemical diversity. In vitro assays using ethanol\u2013water extract (EWE) and isolated compounds with rat liver microsomes demonstrated inhibitory activity against glucose-6-phosphatase (G6Pase), particularly among ent\u2013clerodane diterpenes (73\u201396%), with EWE and compounds 1, 4, and 11 showing the highest inhibition. Molecular docking analysis revealed strong interactions between these diterpenoids and the G6PC1 binding pocket, with binding energies comparable to chlorogenic acid (positive control). These findings position C. guatemalensis as a valuable source of bioactive diterpenoids and support the potential of ent-clerodane derivatives as natural G6Pase inhibitors for hyperglycemia management.<\/jats:p>","DOI":"10.3390\/plants15030442","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:12:46Z","timestamp":1770041566000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ent\u2013Clerodane Diterpenoid Inhibitors of Glucose-6-phosphatase from Croton guatemalensis Lotsy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-176X","authenticated-orcid":false,"given":"Sonia Marlen","family":"Escand\u00f3n-Rivera","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 3000, Circuito Exterior S\/N, Coyoac\u00e1n, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1638-3443","authenticated-orcid":false,"given":"Adolfo","family":"Andrade-Cetto","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 3000, Circuito Exterior S\/N, Coyoac\u00e1n, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6076-2320","authenticated-orcid":false,"given":"Daniel Genaro","family":"Rosas-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 3000, Circuito Exterior S\/N, Coyoac\u00e1n, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-5326","authenticated-orcid":false,"given":"Gerardo","family":"Mata-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 3000, Circuito Exterior S\/N, Coyoac\u00e1n, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-4770","authenticated-orcid":false,"given":"Roberto","family":"Arregu\u00edn-Espinosa","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 3000, Circuito Exterior S\/N, Coyoac\u00e1n, Ciudad Universitaria, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100746","DOI":"10.1016\/j.phyplu.2025.100746","article-title":"The Croton Genera (Euphorbiaceae) and Its Richness in Chemical Constituents with Potential Range of Applications","volume":"5","author":"Galvis","year":"2025","journal-title":"Phytomed. Plus"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xu, W.H., Liu, W.Y., and Liang, Q. (2018). Chemical Constituents from Croton Species and Their Biological Activities. Molecules, 23.","DOI":"10.3390\/molecules23092333"},{"key":"ref_3","unstructured":"(2025, June 12). International Diabetes Federation IDF Diabetes Atlas 11th Edition\u20142025, Brussels. 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