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Acids and base as a catalyst, and solvents effects were investigated for the synthesis of novel UAAs. This novel method provides inexpensive, practicable, and efficient approach to generate UAAs. The use of UAAs has attracted great interest in the development of therapeutic agents and drug discovery to improve their properties. In this context, in addition to the synthesis of new UAAs, their inhibition effects on important metabolic enzymes of acetylcholinesterase (AChE) and carbonic anhydrases I and II (hCA I and II) enzymes were investigated. The compound <jats:bold>2g<\/jats:bold> showed the best inhibition for CA I and AChE enzymes, while compound <jats:bold>2i<\/jats:bold> exhibited the best inhibition profile against CA II isoenzyme. The inhibition values of these compounds were found as 1.85\u2009\u00b1\u20090.64 for AChE, 0.53\u2009\u00b1\u20090.07 for hCA I, 0.44\u2009\u00b1\u20090.15\u2009\u00b5M for hCA II, respectively, and they showed a stronger inhibitory property than acetazolamide (standard inhibitor for hCA I and II) and tacrine (standard inhibitor for AChE) molecules. The activity of the studied molecule against different proteins that are hCA I (PDB ID: 2CAB), hCA II (PDB ID: 5AML), and AChE (PDB ID: 1OCE) was examined. Finally, the drug properties of the studied molecule were examined by performing absorption, distribution, metabolism, excretion, and toxicity analysis.<\/jats:p>","DOI":"10.1002\/jbt.23837","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T11:45:24Z","timestamp":1725450324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The synthesis of novel unnatural amino acid by intramolecular aza\u2010Michael addition reaction as multitarget enzyme inhibitors"],"prefix":"10.1002","volume":"38","author":[{"given":"Nurg\u00fcl","family":"Abul","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Atat\u00fcrk University  Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burak","family":"T\u00fcz\u00fcn","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Cumhuriyet University  Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-1668","authenticated-orcid":false,"given":"\u0130lhami","family":"G\u00fcl\u00e7in","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Atat\u00fcrk University  Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5598-0443","authenticated-orcid":false,"given":"Ufuk","family":"Atmaca","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences Atat\u00fcrk University  Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00319"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar00055a003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)80840-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00499-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.4c00474"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.696"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211023109"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-019-2642-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2019.130467"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1071\/CH12179"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201000688"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol049026b"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo401640c"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2009.08.021"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11426-023-1605-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.3c02734"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.24820\/ark.5550190.p011.209"},{"key":"e_1_2_9_19_1","first-page":"788","volume":"6","author":"Burgess E. 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