{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:58Z","timestamp":1789016878324,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009894","name":"Lodz University of Technology","doi-asserted-by":"publisher","award":["W3\/5P\/2022"],"award-info":[{"award-number":["W3\/5P\/2022"]}],"id":[{"id":"10.13039\/501100009894","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009894","name":"Lodz University of Technology","doi-asserted-by":"publisher","award":["W-3D\/FMN\/5G\/2022"],"award-info":[{"award-number":["W-3D\/FMN\/5G\/2022"]}],"id":[{"id":"10.13039\/501100009894","id-type":"DOI","asserted-by":"publisher"}]},{"award":["W3\/5P\/2022"],"award-info":[{"award-number":["W3\/5P\/2022"]}],"id":[{"id":"https:\/\/ror.org\/00s8fpf52","id-type":"ROR","asserted-by":"publisher"}]},{"award":["W-3D\/FMN\/5G\/2022"],"award-info":[{"award-number":["W-3D\/FMN\/5G\/2022"]}],"id":[{"id":"https:\/\/ror.org\/00s8fpf52","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The search for new compounds capable of inhibiting the activity of enzymes involved in the development of neurodegenerative diseases, including Alzheimer\u2019s disease, has attracted continuing interest for many years. Natural isothiocyanates and their synthetic analogs, as well as compounds containing a 1,3,5-triazine core, constitute a group of molecules with complex mechanisms of action involving multiple molecular targets. Although literature data confirm the activity of both isothiocyanates and s-triazines, these two active fragments have not yet been combined, and it remains unclear whether a synergistic effect can be achieved. In this study, 11 novel isothiocyanate\u2013triazine conjugates, consisting of a 1,3,5-triazine core substituted with aliphatic or cyclic secondary amines and a phosphorus analogue of isothiocyanate [6-(isothiocyanatohexyl)phosphonate)ethyl], were synthesized with yields of 46\u201380%. The pharmacokinetic profiles and parameters related to Lipinski\u2019s rule of five were determined for all compounds. All compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and \u03b2-secretase (BACE1). Compound 1i showed the highest inhibitory activity against AChE (IC50 = 0.182 \u00b1 0.02 \u00b5M), while compound 1b exhibited the strongest inhibition of BACE1 (IC50 = 8.48 \u00b1 2.18 \u00b5M). To explore the potential of these multifunctional derivatives, plausible enzyme-ligand binding models were proposed based on molecular docking simulations.<\/jats:p>","DOI":"10.3390\/biom16091280","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:21Z","timestamp":1788452481000},"page":"1280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Biological Activity of Isothiocyanate-Triazine Conjugates as AChE and BACE1 Inhibitors"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9796-3886","authenticated-orcid":false,"given":"Kacper","family":"G\u00f3recki","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3266-4142","authenticated-orcid":false,"given":"Jakub","family":"Polakowski","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Wi\u0119ckowska","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-2409","authenticated-orcid":false,"given":"Renata","family":"Grzywa","sequence":"additional","affiliation":[{"name":"Department of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Fr\u0105czyk","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-947X","authenticated-orcid":false,"given":"Beata","family":"Kolesi\u0144ska","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4493-1547","authenticated-orcid":false,"given":"Agnieszka","family":"Wr\u00f3bel-Ta\u0142a\u0142aj","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University, 2a Mickiewicza Str., 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-0480","authenticated-orcid":false,"given":"Danuta","family":"Drozdowska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University, 2a Mickiewicza Str., 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4689-1622","authenticated-orcid":false,"given":"\u0141ukasz","family":"Janczewski","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 116 \u017beromskiego Str., 90-924 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Disease International (2024). 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