{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:03:24Z","timestamp":1788329004827,"version":"build-2803163510"},"reference-count":89,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, memory impairment, cognitive dysfunction, and speech impairment. The utility of cholinergic replacement by acetylcholinesterase (AChE) inhibitors in AD treatment has been well documented so far. Recently, studies have also evidenced that human carbonic anhydrases (hCAs) serve as an important target for AD treatment. In this direction, the improvement of new multitarget drugs, which can simultaneously modulate several mechanisms or targets included in the AD pathway, may be a potent strategy to treat AD. In light of these data for understanding and developing AD\u2010related multitarget AChE and hCAs inhibitors, in this study, novel methylene\u2010aminobenzoic acid and tetrahydroisoquinolynyl\u2010benzoic acid derivatives (\n                    <jats:bold>4a<\/jats:bold>\n                    \u2013\n                    <jats:bold>g<\/jats:bold>\n                    and\n                    <jats:bold>6a<\/jats:bold>\n                    \u2013\n                    <jats:bold>g<\/jats:bold>\n                    ) were designed. The synthesized analogs were experimentally validated for their effects by in vitro and direct enzymatic tests. Also, the compounds were subjected to in silico monitoring with\u00a0Schr\u00f6dinger Suite software to assign binding affinities of potential derivatives based on Glide XP scoring, molecular mechanics\u2010generalized Born surface area computing, and validation by molecular docking. The results revealed that\n                    <jats:bold>6c<\/jats:bold>\n                    (1,3\u2010dimethyldihydropyrimidine\u20102,4\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    ,3\n                    <jats:italic>H<\/jats:italic>\n                    )\u2010dione\u2010substituted,\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>I<\/jats:sub>\n                    \u00a0value of 33.00\u2009\u00b1\u20090.29\u2009nM),\n                    <jats:bold>6e<\/jats:bold>\n                    (cyclohexanone\u2010substituted,\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>I<\/jats:sub>\n                    \u00a0value of 18.78\u2009\u00b1\u20090.09\u2009nM), and\n                    <jats:bold>6f<\/jats:bold>\n                    (2,2\u2010dimethyl\u20101,3\u2010dioxan\u20104\u2010one\u2010substituted,\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>I<\/jats:sub>\n                    \u00a0value of 13.62\u2009\u00b1\u20090.21\u2009nM) from the benzoic acid derivatives in this series were the most promising derivatives, as they exhibited a good multifunctional inhibition at all experimental levels and in the in silico validation against hCA I, hCA II, and AChE, respectively, for the treatment of AD.\n                  <\/jats:p>","DOI":"10.1002\/ardp.202000282","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T08:33:00Z","timestamp":1604651580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Novel benzoic acid derivatives: Synthesis and biological evaluation as multitarget acetylcholinesterase and carbonic anhydrase inhibitors"],"prefix":"10.1002","volume":"354","author":[{"given":"Muharrem","family":"Kalayc\u0131","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Arts and Sciences Sakarya University  Sakarya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-2789","authenticated-orcid":false,"given":"C\u00fcneyt","family":"T\u00fcrke\u015f","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Erzincan Binali Y\u0131ld\u0131r\u0131m University  Erzincan Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-4374","authenticated-orcid":false,"given":"Mustafa","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Arts and Sciences Sakarya University  Sakarya Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeliz","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Services, Nihat Delibalta G\u00f6le Vocational High School Ardahan University  Ardahan Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015e\u00fckr\u00fc","family":"Beydemir","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Anadolu University  Eski\u015fehir Turkey"},{"name":"The Rectorate of Bilecik \u015eeyh Edebali University  Bilecik Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2016.05.015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.12.271"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.12.064"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.05.109"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2015.05.034"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2020.101711"},{"key":"e_1_2_7_8_1","first-page":"515","volume":"44","author":"Demir Y.","year":"2016","journal-title":"Hacettepe J. 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