Design, synthesis, characterization, and antioxidant activity studies of novel thienyl-pyrazoles

Abstract

In a sustained search for novel and effective antioxidants, a potential therapeutic leads against renal, and neurological disorders. Amongst the heterocycles, pyrazole and their derivatives have been extensively studied for their biological potencies, particularly to a larger extent for their antioxidant properties. Although many of pyrazole derivatives displayed antioxidant activities, still there is a need of developing efficient protocol for their synthesis, involving ecofriendly conditions, molecules of greater antioxidant efficacy and lesser toxicity, etc. In this context, the current study presents an amberlyst-15 catalysed efficient synthesis of 2-pyrazoline derivatives, 5(a-g) via (3 + 2) annulation of chalcones with phenylhydrazines. Structure proofs of new pyrazoles offered by spectral studies, and the molecular structure of compound 5d of the series by crystallographic studies, which revealed an intra molecular hydrogen bond interactions (C–H⋯N type), and stabilization by C–H...π and π---π molecular interactions. Of the series, compounds 5g and 5h show excellent DPPH (IC50 = 0.245 ± 0.01, and 0.284 ± 0.02 μM); and hydroxyl (IC50 = 0.905 ± 0.01, and 0.892 ± 0.01μM) radical scavenging activities comparable with respective controls, ascorbic acid (IC50 = 0.483 ± 0.01μM) and BHA (IC50 = 1.739 ± 0.01μM). The molecular docking and ADME/Tox studies indicate that, these compounds have good antioxidant activity through π-π stacking with Catalase via Try337 and Phe140, and therefore, might be lead antioxidants for further study.

Keywords

• Amberlyst-15
• Annulation
• Antioxidant
• Hydroxyl
• Chalcone
• Docking