{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:59:36Z","timestamp":1785218376626,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diseases such as Alzheimer's, Parkinson's, and depression result from neurotransmitter imbalances. In particular, for AD, it is critical to inhibit AChE to preserve the decline in acetylcholine levels and to block excessive MAO\u2010B activity, which leads to nerve damage and cognitive impairment. As current scientific research has moved away from the \u201cone drug for one target\u201d approach toward a \u201cmulti\u2010target\u201d strategy, dual\u2010acting inhibitors that simultaneously inhibit both AChE and MAO\u2010B enzymes are considered the most promising new drug candidates for the treatment of Alzheimer's disease. In this study, we investigated the inhibition of AChE, BChE, MAO\u2010A, and MAO\u2010B in the pathophysiology of AD as a working group. Within the scope, 10 new compounds (\n                    <jats:bold>5a<\/jats:bold>\n                    \u2013\n                    <jats:bold>j<\/jats:bold>\n                    ) were synthesized, consisting of a phenolic ring, a secondary or tertiary amine tail, and a 1,2,4\u2010triazole core. The cholinesterase and MAO inhibitory profiles of the compounds were investigated using both in\u00a0vitro and\n                    <jats:italic>in silico<\/jats:italic>\n                    methods. Compound\n                    <jats:bold>5b<\/jats:bold>\n                    exhibited dual inhibitory activity against AChE and MAO\u2010B enzymes, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.136\u2009\u00b1\u20090.006\u2009\u03bcM and 0.108\u2009\u00b1\u20090.005\u2009\u03bcM, respectively. In accordance with\n                    <jats:bold>5b<\/jats:bold>\n                    , it interacted with crucial amino acids of the\n                    <jats:italic>h<\/jats:italic>\n                    AChE and\n                    <jats:italic>h<\/jats:italic>\n                    MAO\u2010B enzymes in the docking studies. These results suggest that\n                    <jats:bold>5b<\/jats:bold>\n                    is a dual\u2010target inhibitor of AChE and MAO\u2010B and represents a promising therapeutic option for the treatment of Alzheimer's disease.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70347","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:28:22Z","timestamp":1784021302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2010Guided Optimization of 1,2,4\u2010Triazole\u2010Thione\u2010Based Mannich Derivatives as Dual\u2010Target Modulators:\n                    <scp>AChE<\/scp>\n                    \/\n                    <scp>MAO<\/scp>\n                    \u2010B"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5339-6940","authenticated-orcid":false,"given":"Hasan Erdin\u00e7","family":"Sellitepe","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Karadeniz Technical University  Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-6474","authenticated-orcid":false,"given":"Ahmet Bu\u011fra","family":"Aksel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Karadeniz Technical University  Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-9383","authenticated-orcid":false,"given":"Hilal","family":"Z\u0131val\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Karadeniz Technical University  Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-7721","authenticated-orcid":false,"given":"Ezgi","family":"Pehlivanlar Yavrucu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Karadeniz Technical University  Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-6266","authenticated-orcid":false,"given":"Beg\u00fcm Nurpelin","family":"Sa\u011fl\u0131k \u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Anadolu University  Eski\u015fehir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-1747","authenticated-orcid":false,"given":"\u0130nci Selin","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Karadeniz Technical University  Trabzon T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5047-7251","authenticated-orcid":false,"given":"Kutsal","family":"\u00d6zcan Kosif","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy Karadeniz Technical University  Trabzon 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