Pyrazoline Derivatives: Synthesis, In Silico, Enzyme Kinetics Studies and Biological Activity against Cholinesterase, Lipoxygenase, and α‐Amylase

Nucleophilic cyclization of the α, β‐unsaturated carbonyl framework of the prepared ( E )‐4‐(3‐bromo‐4‐hydroxy‐5‐methoxyphenyl)but‐3‐en‐2‐one with various hydrazine derivatives to afford their corresponding pyrazolines has been achieved. The enzyme assays conducted showed significant α‐amylase inhibitory activity for 4b with IC 50 value of 2.7 µM. On the other hand, 4a and 4b exhibited IC 50 values of 8.1 µM and 7.5 µM, respectively, against BChE. Significant inhibitory activity against LOX‐15 was also observed by 4c (6.3 µM) and 4 h (5.1 µM). The MTT assay conducted revealed that the most active compounds ( 4b , 4e, and 4 h ) were non‐toxic against the kidney cells. Enzyme kinetics studies performed on the most active compound 4e against BChE revealed a noncompetitive mode of inhibition against this enzyme. The molecular docking studies showed that the compounds had good binding scores with highest score of −5.20 kcal/mol for 4b . Molecular dynamics (MD) conducted, on the other hand, suggested good stability for the compounds, being below 2.4 Å. More importantly, ADME (Absorption, Distribution, Metabolism, and Excretion) studies were conducted to predict the drug likeliness of the compounds. The results reveal that pyrazoline derivatives could potentially serve as a suitable drug candidate for the development of lead molecules for the prevention of Alzheimer disease.