Synthesis, Characterization, Molecular Docking Studies and Biological Evaluation of Some Novel 3,5-disubstituted-1-phenyl-4,5-dihydro-1H-pyrazole Derivatives

Abstract

Abstract: In this study, some new pyrazoline derivatives bearing cyano or nitro groups were synthesized. The structures of the compounds were characterized by IR, 1H-NMR, 13C-NMR and elemental analysis data. The ABTS·+, DPPH·, CUPRAC and β-Carotene/linoleic acid assays were carried out to determine the antioxidant activity of the synthesized pyrazolines. Compound P14 showed higher antioxidant activity than the standard substance BHA with IC50 values of 1.71±0.31 μM and 0.29±0.04 μM in ABTS+ and β-carotene/linoleic acid assays, respectively. Compound P12 also exhibited higher antioxidant activities than BHA with an IC50 value of 0.36±0.14 μM in β-carotene/linoleic acid analysis. In activity studies of pyrazolines against cholinesterase (AChE and BChE), tyrosinase, α-amylase and α- glucosidase, compound P1 (IC50 = 39.51±3.80 μM) showed higher activity against α-amylase and compounds P5 and P12 displayed higher activity against α-glucosidase than acarbose with IC50 values of 14.09±0.62 and 83.26±2.57 μM, respectively. The drug-like properties such as Lipinski and Veber, bioavailability and toxicity risks of the synthesized compounds were also evaluated. The compounds were predicted to be compatible with Lipinski and Veber rules, have high bioavailability and low toxicity profiles. Moreover, molecular docking studies were performed to better understand the high activity of the compounds against a-amylase and a-glucosidase enzymes.