{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:55:22Z","timestamp":1791492922542,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Computational Center of the University of Bialystok","award":["GO-008"],"award-info":[{"award-number":["GO-008"]}]},{"name":"Computational Center of the University of Bialystok","award":["SUB\/2\/DN\/22\/002\/2204"],"award-info":[{"award-number":["SUB\/2\/DN\/22\/002\/2204"]}]},{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok, Poland","doi-asserted-by":"publisher","award":["GO-008"],"award-info":[{"award-number":["GO-008"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok, Poland","doi-asserted-by":"publisher","award":["SUB\/2\/DN\/22\/002\/2204"],"award-info":[{"award-number":["SUB\/2\/DN\/22\/002\/2204"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The synthesis of eleven new and previously undescribed benzamides was designed. These compounds were specifically projected as potential inhibitors of the enzymes acetylcholinesterase (AChE) and \u03b2-secretase (BACE1). N,N\u2032-(1,4-phenylene)bis(3-methoxybenzamide) was most active against AChE, with an inhibitory concentration of AChE IC50 = 0.056 \u00b5M, while the IC50 for donepezil was 0.046 \u00b5M. This compound was also the most active against the BACE1 enzyme. The IC50 value was 9.01 \u00b5M compared to that for quercetin, with IC50 = 4.89 \u00b5M. Quantitative results identified this derivative to be the most promising. Molecular modeling was performed to elucidate the potential mechanism of action of this compound. Dynamic simulations showed that new ligands only had a limited stabilizing effect on AChE, but all clearly reduced the flexibility of the enzyme. It can, therefore, be concluded that a possible mechanism of inhibition increases the stiffness and decreases the flexibility of the enzyme, which obviously impedes its proper function. An analysis of the H-bonding patterns suggests a different mechanism (from other ligands) when interacting the most active derivative with the enzyme.<\/jats:p>","DOI":"10.3390\/ijms241914901","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T11:58:57Z","timestamp":1696420737000},"page":"14901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["New Benzamides as Multi-Targeted Compounds: A Study on Synthesis, AChE and BACE1 Inhibitory Activity and Molecular Docking"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-0480","authenticated-orcid":false,"given":"Danuta","family":"Drozdowska","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Bia\u0142ystok, Mickiewicza Street 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-081X","authenticated-orcid":false,"given":"Dawid","family":"Maliszewski","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Bia\u0142ystok, Mickiewicza Street 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4493-1547","authenticated-orcid":false,"given":"Agnieszka","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Bia\u0142ystok, Mickiewicza Street 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-1871","authenticated-orcid":false,"given":"Artur","family":"Ratkiewicz","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K Street, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Sienkiewicz","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Chemistry, University of Bia\u0142ystok, Cio\u0142kowskiego 1K Street, 15-245 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.tips.2020.04.008","article-title":"A Perspective on multi-target drugs for Alzheimer\u2019s disease","volume":"41","author":"Benek","year":"2020","journal-title":"Trends Pharmacol. 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