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 1 HNMR, 13 C 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 IC 50 =0.81±0.20 μM for α‐glucosidase and IC 50 =1.00±0.05 μM for α‐amylase compared with the standard therapeutic drug acarbose which shows IC 50 =1.30±0.06 μM and IC 50 =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.