{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:47:55Z","timestamp":1785923275946,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID Chile","award":["Fondecyt 1220831"],"award-info":[{"award-number":["Fondecyt 1220831"]}]},{"name":"ANID Chile","award":["Fondecyt 11250944"],"award-info":[{"award-number":["Fondecyt 11250944"]}]},{"award":["Fondecyt 1220831"],"award-info":[{"award-number":["Fondecyt 1220831"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Fondecyt 11250944"],"award-info":[{"award-number":["Fondecyt 11250944"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fondequip Chile","award":["LF-NMR 80 (EQM220161)"],"award-info":[{"award-number":["LF-NMR 80 (EQM220161)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Polygodial (9), a drimane sesquiterpene dialdehyde from Drimys winteri, has not previously been examined against carbohydrate-hydrolyzing enzymes. Methods: Regioselective Wittig olefination at C12 gave the enoate 10; reduction of the remaining C11 aldehyde with NaBH4 was followed by spontaneous intramolecular conjugate addition, affording the annellated tetrahydrofuran 12a and the bridged ether 12b. Results: All three derivatives inhibited \u03b1-glucosidase and \u03b1-amylase more strongly than the parent compound. Compound 12a was the most active \u03b1-glucosidase inhibitor (IC50 = 53.98 \u00b1 3.0 \u00b5M, against 90.36 \u00b1 4.0 \u00b5M for acarbose) and, in docking, the only derivative to occupy the acarbose-binding site of the enzyme (\u22128.1 kcal\/mol). However, this 12a\u2013\u03b1-glucosidase pose was not maintained during the 200 ns simulations. The enoate 10 was the most active \u03b1-amylase inhibitor (IC50 = 42.32 \u00b1 2.1 \u00b5M, against 78.24 \u00b1 3.9 \u00b5M for acarbose; \u22128.5 kcal\/mol). Over 200 ns of molecular dynamics, the 10\u2013\u03b1-amylase complex remained associated, with binding attributed by MM-GBSA mainly to van der Waals and lipophilic terms. Conclusions: Converting the dialdehyde into an enoate or a cyclic ether increases carbohydrase inhibition and determines which of the two enzymes is preferentially inhibited.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080960","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Semisynthetic Derivatives of Polygodial as \u03b1-Glucosidase and \u03b1-Amylase Inhibitors: In Vitro Evaluation, Molecular Docking and Molecular Dynamics Simulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Viviana","family":"Burgos","sequence":"first","affiliation":[{"name":"Escuela de Tecnolog\u00eda M\u00e9dica, Facultad de Salud, Universidad Santo Tom\u00e1s, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9066-1763","authenticated-orcid":false,"given":"Cecilia","family":"Villegas","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas y Qu\u00edmicas, Facultad de Recursos Naturales, Universidad Cat\u00f3lica de Temuco, Rudecindo Ortega, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Sanzana","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products & Drug Discovery, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Oporto","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products & Drug Discovery, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-6069","authenticated-orcid":false,"given":"Bernd","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie, Universit\u00e4t Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-9260","authenticated-orcid":false,"given":"Vaderament-Alexe","family":"Nchiozem-Ngnitedem","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Chemie, Universit\u00e4t Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2913-1765","authenticated-orcid":false,"given":"Muhammad Javid","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products & Drug Discovery, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4668-4984","authenticated-orcid":false,"given":"Cristian","family":"Paz","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products & Drug Discovery, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global Aetiology and Epidemiology of Type 2 Diabetes Mellitus and Its Complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat. 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