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In this study, eight hexahydro\u20105<jats:italic>H<\/jats:italic>\u2010isoxazolo[4,5\u2010<jats:italic>f<\/jats:italic>]isoindole\u20105,7(6<jats:italic>H<\/jats:italic>)\u2010dione derivatives bearing isoxazole moieties were synthesized and their inhibitory effects on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoforms I and II (hCA I and hCA II), which are associated with global disorders such as Alzheimer's disease (AD), epilepsy, and glaucoma, were investigated. Among the synthesized compounds, derivatives <jats:bold>9\u201312<\/jats:bold> exhibited notable inhibitory activity against AChE, hCA I, and hCA II enzymes. The IC<jats:sub>50<\/jats:sub> values were determined to be in the ranges of 4.65\u201312.83\u2009nM for AChE, 23.17\u201379.58\u2009nM for hCA I, and 36.58\u201388.28\u2009nM for hCA II. Molecular docking studies of the synthesized compounds <jats:bold>9a\u201312a<\/jats:bold> were carried out against three proteins: 1AZM (Human carbonic anhydrase I), 5AML (three\u2010dimensional structure of human carbonic anhydrase II) and 4EY6 (recombinant human acetylcholinesterase). AZA and Tacrine were used as references in the docking analyses. All compounds were determined to have a higher binding affinity than Tacrine (\u22127.04\u2009kcal\/mol) and AZA (\u22126.12 and \u22126.24\u2009kcal\/mol). The results of inhibition tests showed that some isoxazole derivatives (<jats:bold>9\u201312<\/jats:bold>) showed significant inhibitory effects against both CA and AChE enzymes.<\/jats:p>","DOI":"10.1002\/jbt.70550","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:44Z","timestamp":1760113844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Isoindole\u20101,3\u2010Dione\u2010Isoxazole Hybrids: Synthesis, Characterization, Evaluation of Their Inhibitory Activities on Carbonic Anhydrase and Acetylcholinesterase"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-9674","authenticated-orcid":false,"given":"\u00d6zlem G\u00fcndo\u011fdu","family":"Ayta\u00e7","sequence":"first","affiliation":[{"name":"Department of Food Technology, Kaman Vocational School Ahi Evran University Kirsehir 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