Kaya_2025_ACS.Omega_10_38427

Ten novel pyrazoline-thiazole derivatives were synthesized and assessed for their potential as acetylcholinesterase and butyrylcholinesterase inhibitors. The structure of the target compounds was characterized by (1)H NMR and (13)C NMR, and purity was determined using HPLC. The in vitro enzyme inhibitory activity assays determined that compounds 3f (IC(50) = 0.382 microM) and 3g (IC(50) = 0.338 microM) showed good inhibitory activity of acetylcholinesterase (AChE). Compound 3f has a selective inhibitory effect on AChE, while compound 3g has a dual effect, being effective against both AChE and BChE (IC(50) = 2.087 microM). The molecular docking results of compound 3g with high inhibitory activity for AChE experimentally showed that it has a strong inhibitory effect close to that of the reference inhibitor tacrine. The compound 3g was found to have the highest activity in its interaction with the BChE (4BDS) protein with a low docking score (-5.555 kcal/mol). Furthermore, the prediction of ADME properties of compounds 3f and 3g was determined through Swiss ADME.