Exploring 2-Pyrazoline derivatives as potent antidiabetic agents and cholinesterase inhibitors: Their synthesis and molecular docking studies

Herein, unique pyrazoline derivatives were synthesized, and their structures were elucidated by various spectroscopic techniques. Moreover, potential in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-glucosidase, and alpha-amylase inhibition effects of the compounds were also investigated. Molecular docking studies were performed to further elucidate the enzyme inhibitory activities. The compound 2c (IC50 = 1.64 +/- 0.04 and 4.18 +/- 0.22 mu M, respectively) exhibited the strongest inhibitory activity against AChE and BChE, while compounds 2 m (IC50 = 4.29 +/- 0.20 mu M) and 2i (IC50 = 4.31 +/- 0.08 mu M) showed promising AChE inhibitory activity. On the other hand, compounds 2a (IC50= 5.01 +/- 0.13 mu M) and 2i (IC50 = 5.06 +/- 0.72 mu M) significantly inhibited BChE. In addition, all compounds except 2c and 2f showed great inhibitory activity against alpha-amylase at lower concentrations compared to acarbose (IC50 = 72.57 +/- 3.16 mu M). Similarly, all compounds except 2k exhibited higher inhibitory activity than acarbose (IC50 = 207.08 +/- 12.20 mu M) against alpha-glucosidase. Among the compounds, 2a (IC50 = 15.05 +/- 5.64 mu M), 2b (IC50 = 14.34 +/- 5.05 mu M), and 2e (IC50 = 11.72 +/- 0.46 mu M) had excellent inhibitory activity at certain concentrations. The data obtained from the molecular docking studies supported inhibitory activity results. This study presents potential leads for the development of antidiabetic and Alzheimer's therapeutics.