Synthesis of Pyrazoline-Embedded 1,2,3-Triazole Derivatives via 1,3-Dipolar Cycloaddition Reactions with in vitro and in silico Studies

A series of hybrid molecules containing pyrazolines and 1,2,3-triazoles have been synthesized via Cu(I) mediated 1,3-dipolar cycloaddition reactions bearing para substituted azides and dipolarophile (acetylenes) as a reactive precursors. Structure of all the synthesized derivatives were confirmed by (HNMR)-H-1, (CNMR)-C-13, LC-MS and IR spectral analysis and they are screened for a-glucosidase and alpha-amylase inhibitory and antioxidant activities by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)) methods. Among the synthesized compounds, 3-(4-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-(4-fluorophenyl)-4,5-dihydropyrazole-1-carbaldehyde (5k) showed promising inhibition of the antidiabetic enzymes with IC50= 0.81 +/- 0.20 mu M for alpha-glucosidase and IC50= 1.00 +/- 0.05 mu M for alpha-amylase compared with the standard therapeutic drug acarbose which shows IC50= 1.30 +/- 0.06 mu M and IC50= 0.75 +/- 0.08 mu M for alpha-glucosidase and alpha-amylase. Compared to all the synthesized compounds, the bleeching ability of 3-(4-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-(4-fluorophenyl)-4,5-dihydropyrazole-1-carbaldehyde (5 k) showed promising antioxidant activity in comparison with standard Butylated hydroxyl anisole. The molecular docking studies revealed the compound 3-(4-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-(4-fluorophenyl)-4,5-dihydropyrazole-1-carbaldehyde having lower binding energy with the maximum efficacy.