{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:33:45Z","timestamp":1784014425923,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T00:00:00Z","timestamp":1694908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) presents a multifactorial neurological disorder with multiple enzyme involvement in its onset. Conventional monotherapies fall short in providing long\u2010term relief, necessitating the exploration of alternative multitargeting approaches to address the complexity of AD. Therefore, the design, synthesis, and in vitro and in silico evaluation of 2\u2010oxoquinoline\u2010based thiosemicarbazones <jats:bold>9a\u2013r<\/jats:bold> as multipotent analogs, able to simultaneously inhibit the cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of AD, are reported. In the in vitro experimental evaluation of MAO and ChE inhibition, all tested compounds demonstrated remarkable potency exhibiting nonselective inhibition of both MAO\u2010A and MAO\u2010B, and selective inhibition of acetylcholinesterase (AChE) over butyrylcholinesterase (BChE), with <jats:bold>9d<\/jats:bold>, <jats:bold>9j<\/jats:bold>, and <jats:bold>9m<\/jats:bold> evolving as lead compounds for MAO\u2010A, MAO\u2010B, and AChE, displaying IC<jats:sub>50<\/jats:sub> values of 0.35\u2009\u00b1\u20090.92, 0.50\u2009\u00b1\u20090.02, and 0.25\u2009\u00b1\u20090.13\u2009\u03bcM, respectively. Moreover, the kinetic studies revealed that all tested compounds inhibited all three enzymes through a competitive mode of inhibition. Furthermore, the molecular docking studies of the most active compounds revealed several crucial interactions, particularly hydrogen bonding interactions. These interactions were observed between the nitrogen and sulfur atoms of thiosemicarbazone and the nitrogen and oxygen atoms of the quinoline ring with various amino acids, suggesting the strong interactions of these compounds with the enzymes.<\/jats:p>","DOI":"10.1002\/ardp.202300430","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T03:00:35Z","timestamp":1695006035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["2\u2010Oxoquinoline\u2010based\u2010thiosemicarbazones as multitargeting neurotherapeutics against Alzheimer's disease: In vitro and in silico studies of MAO and ChE inhibitors"],"prefix":"10.1002","volume":"356","author":[{"given":"Rabia","family":"Basri","sequence":"first","affiliation":[{"name":"Institute of Chemical Sciences Bahauddin Zakariya University  Multan 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