Mechanistic insights and therapeutic implications of novel pyrazoline derivatives on antioxidant and enzymatic inhibitory activities.

• Synthesis of four pyrazoline derivatives. • Anti-oxidant, tyrosinase, and acetylcholinesterase activities were screened. • DFT/B3LYP quantum chemical computation method was applied. • Prediction of drug-likeness and ADMET profile with the aid of in silico methods. • Molecular docking analysis reinforced the experimental results. One of the major features of medicinal chemistry, is the synthesis of novel compounds, and the assessment of their biological activities for potential therapeutic applications. As a contribution to this filed of interest, the present work examines the effects of newly synthesized pyrazoline derivatives. To this end, four pyrazoline derivatives were synthesized and evaluated for their antioxidant activities and enzymatic inhibitory in vitro against acetylcholinesterase (AChE) and tyrosinase. All the synthetized compounds 2a–2d all displayed a moderate to potent antioxidant activity. For the enzymatic inhibitory activity, compound 2a exerted the most potent acetylcholinesterase inhibition with an IC 50 value of (IC 50 = 3.93 ± 0.52 µM) which is twice greater than the standard drug, Galantamine (IC 50 = 6.27 ± 1.15 µM), whereas, compound 2a was determined as the best inhibitor among the synthesized compounds for the tyrosinase enzyme with an IC 50 value of (32.65 ± 2.30 μM). Density Functional Theory (DFT) calculations were performed to determine the compound's properties, and molecular docking studies were conducted to discuss potential interactions between the most active compound (2a) and active sites of proteins AChE (PDB: 1ACL) and tyrosinase (PDB: 2Y9X). Based on in silico predictions of Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) and pharmacokinetic parameters, it is suggested that these compounds could potentially exhibit favorable oral bioavailability. The paper offers promising insights into the therapeutic potential of these pyrazoline derivatives, particularly compound 2a. It encourages further investigation into the practical application of these findings, possibly leading to new therapeutic avenues in the treatment of diseases associated with acetylcholinesterase and tyrosinase. [Display omitted] [ABSTRACT FROM AUTHOR]