Design, Synthesis, and Molecular Docking Studies of Novel Pyrazoline-Thiazoles as Cholinesterase Dual-Target Inhibitors for the Treatment of Alzheimer’s Disease

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 ¹H NMR and ¹³C NMR, and purity was determined using HPLC. The in vitro enzyme inhibitory activity assays determined that compounds <b>3f</b> (IC₅₀ = 0.382 μM) and <b>3g</b> (IC₅₀ = 0.338 μM) showed good inhibitory activity of acetylcholinesterase (AChE). Compound <b>3f</b> has a selective inhibitory effect on AChE, while compound <b>3g</b> has a dual effect, being effective against both AChE and BChE (IC₅₀ = 2.087 μM). The molecular docking results of compound <b>3g</b> 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 <b>3g</b> 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 <b>3f</b> and <b>3g</b> was determined through Swiss ADME.