Antioxidant, anti-inflammatory and anti-glycation activities of some 4-aminoantypyrine derivatives: In vitro and in silico study

Abstract

Aminoantipyrine exhibits antioxidant and anti-inflammatory effects. However, its potential as an anti-glycating agent has not been extensively studied. This research aims to investigate the antioxidant, anti-inflammatory, and anti-glycation properties of specific derivatives of 4-amino antipyrine through experimental and theoretical methods. Thirteen Schiff bases were synthesized by reacting 4-aminoantipyrine with substituted benzaldehydes, and seven ether derivatives were obtained from these Schiff bases via Williamson ether synthesis. The compounds were characterized using FT-IR, UV-visible, EI-MS, and ¹H NMR analyses. Cytotoxicity assessments were conducted using brine shrimp and 3T3 mouse fibroblast cell lines. Molecular descriptors were obtained from Density Functional Theory (DFT) calculations, and molecular docking was used to determine binding affinity. Additionally, in-silico ADMET (adsorption, distribution, metabolism, excretion, and toxicity) screening was performed. The synthesized compounds were evaluated for anti-inflammatory, antioxidant, and anti-glycation properties. The results showed promising activities for three compounds in the anti-inflammatory assay. Five compounds demonstrated significant antioxidant effects, while eight exhibited moderate anti-glycation properties. Compounds S1 and S13 show potential inhibition against the anti-inflammatory, antioxidant, and anti-glycation activities. DFT calculations and molecular docking identified S6, S7, and S9 as the most active compounds. All compounds displayed favorable results in terms of oral bioavailability, lipophilicity, pharmacokinetics, and toxicity prediction. These derivatives of 4-aminoantipyrine were non-toxic and showed potential as drug candidates due to their anti-inflammatory, antioxidant, and anti-glycation properties.