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For this purpose, in this study, 12 compounds including thiosemicarbazone pharmacophore, have been synthesized for the treatment of the Alzheimer's disease. 3,4\u2010Dimethoxybenzene or 1,3\u2010benzodioxolone rings were used for the PAS region. The substituted piperazine benzene structure is preferred for the CAS region. At the same time, the thiosemicarbazone pharmacophore structure with known ChE enzyme inhibition potential was used as a bridge connecting the CAS and PAS regions. Structure determination of compounds <jats:bold>3a\u20133l<\/jats:bold> were revealed using <jats:sup>13<\/jats:sup>C\u2010NMR, <jats:sup>1<\/jats:sup>H\u2010NMR, and HRMS spectroscopic methods. The inhibition profile of obtained compounds (<jats:bold>3a\u20133l<\/jats:bold>) against ChE was evaluated using in vitro modified Ellman method. Compounds <jats:bold>3a<\/jats:bold>, <jats:bold>3b<\/jats:bold>, <jats:bold>3f<\/jats:bold>, <jats:bold>3g<\/jats:bold> and <jats:bold>3i<\/jats:bold> exhibited inhibitory activity against the AChE enzyme. Compound <jats:bold>3a<\/jats:bold> showed the highest inhibitory potential with an IC<jats:sub>50<\/jats:sub>\u2009=\u20090.030\u2009\u00b1\u20090.001\u2009\u03bcM. As a result of molecular docking studies, compound <jats:bold>3a<\/jats:bold> displayed important interactions compared to other active derivatives. Molecular dynamics studies are important to see the stability of the complex formed by ligand and protein. RMSD, RMSF ang Rg parameters were calculated via dynamic studies. In conclusion, compound <jats:bold>3a<\/jats:bold> may be a potential AChE enzyme inhibitor with its strong inhibitory potential and behavior in silico.<\/jats:p>","DOI":"10.1002\/jmr.3059","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T05:30:14Z","timestamp":1695101414000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Design, synthesis, biological activities, and evaluation of molecular docking\u2010dynamics studies of new thiosemicarbazones that may be effective against Alzheimer's disease"],"prefix":"10.1002","volume":"36","author":[{"given":"Neslihan","family":"Conger","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Anadolu University  Eski\u015fehir 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