Eco-friendly polyethylene glycol (PEG-400): PEG mediated synthesis, in-vitro, molecular dynamics, DFT, docking, ADMET and MM-GBSA studies of novel sulfonamides as potential antioxidant agents

Abstract

Novel thiomorpholine bearing sulfonamide analogs 3(a-f) were synthesized by a facile one-pot, single-step process in good to excellent yields (87–95 %). Polyethylene glycol (PEG-400) was used as an eco-friendly, recyclable, and non-flammable solvent. In-vitro antioxidant studies were done using H 2 O 2 and DPPH radical scavenging assays, while the docking studies were carried out using the Maestro software. In the DPPH assay, the activity of compound 3c with an IC 50 value of 30.83±0.33 µg/mL was comparable to the standard, ascorbic acid (13.54±0.33 µg/mL). Interestingly, this compound demonstrated the highest scavenging antioxidant activity at all concentrations, with an IC 50 value of 32.78±0.33 µg/mL in the H 2 O 2 method. Compound 3b, with salt bridge interactions and hydrogen bonds, exhibited a docking score of -2.01 kcal/mol (PDB: 1H4O). ADME results indicated that all the synthesized compounds obeyed Lipinski’s rule, indicating the drug-like properties. The RMSD curve of complex 3b was observed to be closely matching with benzoic acid, the co-crystallized ligand, indicating alignment and stability with the reference ligand. The optimized molecules with lower energy gaps of 2.17, 4.23, and 1.21 eV indicating that the synthesized compounds shown potent biological activity. This pro tocol offers excellent yields, green solvent, catalyst-free, shorter reaction times, inexpensive, and no harsh re action conditions. These research findings reveal that these sulfonamide analogs could be potent antioxidant pharmacophores for future research in antioxidant drug discovery.