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The bis\u2010sulfone derivatives were characterized by <jats:sup>1<\/jats:sup>H\u2010NMR, <jats:sup>13<\/jats:sup>C\u2010NMR, Fourier\u2010transform infrared spectroscopy, and elemental analysis techniques. Nuclear Overhauser effect experiments were performed to determine the orientation of the sulfonyl groups in bis\u2010sulfone derivatives. Here, we report the synthesis and testing of novel bis\u2010sulfone compound\u2013based hybrid scaffold of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the development of novel molecules toward\u00a0the therapy of Alzheimer's disease. The novel synthesized bis\u2010sulfone compounds demonstrated <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> values between 11.4\u2009\u00b1\u20093.4 and 70.7\u2009\u00b1\u200923.2\u2009nM on human carbonic anhydrase I isozyme (hCA I), 28.7\u2009\u00b1\u20096.6 to 77.6\u2009\u00b1\u20095.6\u2009nM on human carbonic anhydrase II isozyme (hCA II), 18.7\u2009\u00b1\u20092.61 to 95.4\u2009\u00b1\u200925.52\u2009nM on AChE, and 9.5\u2009\u00b1\u20092.1 to 95.5\u2009\u00b1\u20091.2\u2009nM on BChE enzymes. The results showed that novel bis\u2010sulfone derivatives can have promising drug potential for glaucoma, leukemia, epilepsy, and Alzheimer's disease, which are associated with the high enzymatic activity of hCA I, hCA II, AChE, and BChE enzymes.<\/jats:p>","DOI":"10.1002\/jbt.22401","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T17:13:17Z","timestamp":1570122797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis of novel bis\u2010sulfone derivatives and their inhibition properties on some metabolic enzymes including carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-1834","authenticated-orcid":false,"given":"Abdullah","family":"Bi\u00e7er","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science Akdeniz University Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4400-2302","authenticated-orcid":false,"given":"R\u00fcya","family":"Kaya","sequence":"additional","affiliation":[{"name":"Central Research and Application Laboratory A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University A\u011fr\u0131 Turkey"},{"name":"Department of Chemistry, Faculty of Science Atat\u00fcrk University Erzurum Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-0705","authenticated-orcid":false,"given":"Bar\u0131\u015f","family":"An\u0131l","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Atat\u00fcrk University Erzurum Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-8344","authenticated-orcid":false,"given":"G\u00fcnseli","family":"Turgut Cin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Akdeniz University Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-1668","authenticated-orcid":false,"given":"\u0130lhami","family":"G\u00fclcin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Atat\u00fcrk University Erzurum Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-729X","authenticated-orcid":false,"given":"Mehmet Serdar","family":"G\u00fcltekin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Atat\u00fcrk University Erzurum Turkey"},{"name":"Faculty of Pharmacy A\u011fr\u0131 \u0130brahim \u00c7e\u00e7en University A\u011fr\u0131 Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,3]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr00038a002"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr990372u"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00068-0"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2006.01.051"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.09.004"},{"key":"e_1_2_6_1_7_1","first-page":"532467","volume":"2014","author":"Abdel\u2010Aziz H. 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