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The DLCs exhibited potent and selective inhibition of MAO\u2010B, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 0.019 to 18.98\u2009\u03bcM, whereas activity toward MAO\u2010A was moderate to low (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.81 to\u2009&gt;\u200920\u2009\u03bcM). Among the tested DLCs,\n                    <jats:bold>DLC9<\/jats:bold>\n                    and\n                    <jats:bold>DLC14<\/jats:bold>\n                    showed the highest MAO\u2010B inhibitory potential with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.054\u2009\u00b1\u20090.004\u2009\u03bcM and 0.019\u2009\u00b1\u20090.0015\u2009\u03bcM, respectively, and high selectivity indexes (&gt;\u2009370 and &gt;\u20091052, respectively), whereas\n                    <jats:bold>DLC12<\/jats:bold>\n                    displayed notable MAO\u2010A inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.81\u2009\u00b1\u20090.035\u2009\u03bcM). Kinetic and reversibility studies revealed that the selected two lead DLCs (\n                    <jats:bold>DLC9<\/jats:bold>\n                    and\n                    <jats:bold>DLC14<\/jats:bold>\n                    ) acted as mixed\u2010type reversible MAO\u2010B inhibitors, with K\n                    <jats:italic>\u1d62<\/jats:italic>\n                    values of 20.0\u2009\u00b1\u20092.83\u2009nM and 10.0\u2009\u00b1\u20092.82\u2009nM, respectively. Furthermore, IC\n                    <jats:sub>50<\/jats:sub>\n                    values of AChE inhibitory activities ranged from 5.40\u2009to\u2009&gt;\u200940\u2009\u00b5M, whereas those of BuChE inhibitory activity range from 4.30 to\u2009&gt;\u200940\u2009\u00b5M.\n                    <jats:bold>DLC6<\/jats:bold>\n                    showed the best AChE inhibitory potential with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 5.40\u2009\u00b1\u20090.29\u2009\u00b5M, while\n                    <jats:bold>DLC13<\/jats:bold>\n                    revealed effective BuChE inhibitory potential with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 4.30\u2009\u00b1\u20090.89\u2009\u00b5M. Molecular docking studies performed on hMAO\u2010A and hMAO\u2010B revealed that\n                    <jats:bold>DLC14<\/jats:bold>\n                    establishes favourable \u03c0\u2013\u03c0 stacking within the aromatic cage of hMAO\u2010B and maintains complementary hydrophobic contacts along the substrate cavity, whereas\n                    <jats:bold>DLC6<\/jats:bold>\n                    lacks this key interaction due to steric interference of the ethoxy substituent. Among the three most potent MAO\u2010B inhibitors (\n                    <jats:bold>DLC2<\/jats:bold>\n                    ,\n                    <jats:bold>DLC9<\/jats:bold>\n                    , and\n                    <jats:bold>DLC14<\/jats:bold>\n                    ),\n                    <jats:bold>DLC2<\/jats:bold>\n                    exhibited the most favourable microsomal stability with the longest half\u2010life and lowest intrinsic clearance, whereas\n                    <jats:bold>DLC14<\/jats:bold>\n                    showed comparable metabolic profiles in rat and human liver microsomes. Experimental BBB permeability assays were hindered by compound\u2010membrane interactions; however,\n                    <jats:italic>in silico<\/jats:italic>\n                    predictions indicated satisfactory oral bioavailability and brain penetration for all three candidates. In the\n                    <jats:bold>MPTP<\/jats:bold>\n                    \u2010induced rat model of parkinsonism, the selective MAO\u2010B inhibitor\n                    <jats:bold>DLC14<\/jats:bold>\n                    and the non\u2010selective inhibitor\n                    <jats:bold>DLC6<\/jats:bold>\n                    significantly improved motor deficits and behavioural impairments across open field, pole, bar, rotarod, and forced swim tests, with progressive improvements observed up to Day 28. Notably,\n                    <jats:bold>DLC14<\/jats:bold>\n                    consistently outperformed\n                    <jats:bold>DLC6<\/jats:bold>\n                    and demonstrated an efficacy profile comparable to that of Selegiline, highlighting its therapeutic potential as an antiparkinsonian agent. These results indicate that\n                    <jats:bold>DLC14<\/jats:bold>\n                    is potent and selective MAO\u2010B inhibitor and could serve as promising candidate for the treatment of neurodegenerative disorders, such as Parkinson's disease.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70349","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:09:27Z","timestamp":1784138967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a Potent and Selective MAO\u2010B Inhibitor From a Donepezil\u2010Linked Chalcone Library With Promising Antiparkinsonian Activity"],"prefix":"10.1002","volume":"87","author":[{"given":"Azize","family":"Kirac\u2010Aydin","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science Istanbul University Istanbul T\u00fcrkiye"},{"name":"Institute of Graduate Studies in Science Istanbul University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-8796","authenticated-orcid":false,"given":"Bishnu Prasad","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Pharmacy, Sunchon National University Suncheon Republic of Korea"},{"name":"Department of Chemical Science and Engineering Kathmandu University Kavre Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyajit","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupsa","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abanish","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"Pattnaik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Technology Birla Institute of Technology Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Mondal","sequence":"additional","affiliation":[{"name":"Bioanalysis, Eurofins Advinus Biopharma Services India Pvt. 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