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All new thiazolyl\u2013pyrazolines showed activity at nanomolar levels as\n                    <jats:italic>h<\/jats:italic>\n                    CA I,\n                    <jats:italic>h<\/jats:italic>\n                    CA II, and AChE inhibitors, with\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>I<\/jats:sub>\n                    values in the range of 13.35\u201363.79, 7.01\u2013115.80, and 17.89\u201348.05\u2009nM, respectively. 1\u2010[4\u2010(4\u2010Cyanophenyl)thiazol\u20102\u2010yl]\u20103\u2010(4\u2010piperidinophenyl)\u20105\u2010(4\u2010fluorophenyl)\u20102\u2010pyrazoline (\n                    <jats:bold>4f<\/jats:bold>\n                    ) and 1\u2010(4\u2010phenylthiazol\u20102\u2010yl)\u20103\u2010(4\u2010piperidinophenyl)\u20105\u2010(4\u2010fluorophenyl)\u20102\u2010pyrazoline (\n                    <jats:bold>4a<\/jats:bold>\n                    ) against\n                    <jats:italic>h<\/jats:italic>\n                    CAs and 1\u2010[4\u2010(4\u2010chlorophenyl)thiazol\u20102\u2010yl]\u20103\u2010(4\u2010piperidinophenyl)\u20105\u2010(4\u2010fluorophenyl)\u20102\u2010pyrazoline (\n                    <jats:bold>4d<\/jats:bold>\n                    ) and 1\u2010[4\u2010(4\u2010nitrophenyl)thiazol\u20102\u2010yl]\u20103\u2010(4\u2010piperidinophenyl)\u20105\u2010(4\u2010fluorophenyl)\u20102\u2010pyrazoline (\n                    <jats:bold>4b<\/jats:bold>\n                    ) against AChE were identified as highly potent inhibitors, superior to the standard drugs, acetazolamide and tacrine, respectively. Compounds\n                    <jats:bold>4a\u2013k<\/jats:bold>\n                    were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. Moreover, a comprehensive ligand\u2013receptor interaction prediction was performed using the ADME\u2010Tox, Glide XP, and MM\u2010GBSA modules of the Schr\u00f6dinger Small\u2010Molecule Drug Discovery Suite to elucidate the potential binding modes of the new hybrid inhibitors against these metabolic enzymes.\n                  <\/jats:p>","DOI":"10.1002\/ardp.202100294","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T20:24:42Z","timestamp":1632774282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds"],"prefix":"10.1002","volume":"354","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy 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Vocational High School Ardahan University Ardahan Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9535-2508","authenticated-orcid":false,"given":"G\u00fcl\u015fen","family":"Akal\u0131n \u00c7ift\u00e7i","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Anadolu University Eski\u015fehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-6902","authenticated-orcid":false,"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 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