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

Abstract

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 1HNMR, 13C NMR, LC–MS and IR spectral analysis and they are screened for α-glucosidase and α-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 (5 k) showed promising inhibition of the antidiabetic enzymes with IC50=0.81±0.20 μM for α-glucosidase and IC50=1.00±0.05 μM for α-amylase compared with the standard therapeutic drug acarbose which shows IC50=1.30±0.06 μM and IC50=0.75±0.08 μM for α-glucosidase and α-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.