{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T20:28:53Z","timestamp":1789849733543,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018998","name":"Ege University Research Foundation","doi-asserted-by":"publisher","award":["14\u2010ECZ\u2010044"],"award-info":[{"award-number":["14\u2010ECZ\u2010044"]}],"id":[{"id":"10.13039\/501100018998","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A series of benzimidazoles and its analogs (benzoxazoles and benzothiazoles) bearing a benzohydrazide\u2010hydrazones moiety at the 2\u2010position were designed and synthesized as potential acetylcholinesterase (AChE) inhibitors. Cholinesterase (ChE) inhibitory activity results showed that all compounds displayed good inhibition of AChE, whereas only some of the compounds were active against BChE. Among the title compounds, it was found that all benzimidazole series were selective towards AChE. Kinetic analysis and molecular modeling studies were conducted on the most active compounds, namely\n                    <jats:bold>1j<\/jats:bold>\n                    for AChE and\n                    <jats:bold>3g<\/jats:bold>\n                    for BChE inhibition. The kinetic results showed that the tested compounds exhibited a mixed\u2010type inhibition mechanism on both enzymes. In cell culture studies, all compounds were evaluated for their neuroprotective effects against hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    )\u2010induced oxidative stress in the SH\u2010SY5Y human neuroblastoma cell line. Several compounds demonstrated more than 30% neuroprotection at a low concentration (1\u2009\u03bcM) in the presence of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . Selected compounds, chosen based on their EC\n                    <jats:sub>50<\/jats:sub>\n                    values, were further examined for their effects on glycogen synthase kinase\u20103 beta (GSK3\u03b2), an enzyme whose activity has been reported to be increased in the brains of patients with Alzheimer's disease (AD). The inhibition of GSK3\u03b2 was assessed by measuring phosphorylated GSK3\u03b2 (pGSK3\u03b2, Ser9) protein expression via Western Blot analysis under oxidative stress conditions. Among the tested compounds,\n                    <jats:bold>1l<\/jats:bold>\n                    ,\n                    <jats:bold>2b<\/jats:bold>\n                    ,\n                    <jats:bold>2j<\/jats:bold>\n                    , and\n                    <jats:bold>3l<\/jats:bold>\n                    significantly increased pGSK3\u03b2 (Ser9) protein levels compared to cells treated with tideglusib, a known GSK3\u03b2 inhibitor.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70285","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:15:23Z","timestamp":1775484923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synthesis, Bioactivity and Molecular Modeling Studies on Benzimidazole Derivatives and Its Isosteres as Potent\n                    <scp>AChE<\/scp>\n                    \/\n                    <scp>BChE<\/scp>\n                    and\n                    <scp>GSK3\u03b2<\/scp>\n                    Inhibitors for Alzheimer's Disease"],"prefix":"10.1111","volume":"107","author":[{"given":"G\u00f6zde","family":"Sayar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-5932","authenticated-orcid":false,"given":"Sulunay","family":"Parlar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Hande","family":"Tarikogullari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-444X","authenticated-orcid":false,"given":"Mumin Alper","family":"Erdo\u011fan","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine, Katip Celebi University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guliz","family":"Armagan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy, Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1477-4440","authenticated-orcid":false,"given":"Vildan","family":"Alptuzun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy, Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12861"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.06.065"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201600351"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiolchem.2022.107748"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115680266318722240809050235"},{"key":"e_1_2_10_7_1","unstructured":"Case D. A. K.Belfon I. Y.Ben\u2010Shalom et\u00a0al.2020.\u201cAmber2020. University of California San Francisco USA.\u201d"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm7009364"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2013.05.138"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010016\u20101648\u20101"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00124a002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103299"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174847"},{"issue":"6","key":"e_1_2_10_14_1","first-page":"293","article-title":"Synthesis and Antitumor Activity of Some New N\u2010Substituted\u2010Sulfonyl, 1,2,4\u2010Triazole, N\u2010Substituted\u2010Benzylidene and Pyrrole Derivatives Attached to 4\u2010(Benzo[d]Thiazol\u20102\u2010Yl)Benzohydrazide","volume":"3","author":"El\u2010Hamouly W. 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