Synthesis, Molecular Docking, and Peroxidase Modulatory Activity of Novel Sulphonamide-Functionalised Aspartic Acid Carboxamides

Abstract

<title>Abstract</title> Oxidative stress occurs when the production of oxygen radicals exceeds the neutralizing ability of antioxidants, triggering cellular processes such as apoptosis, tumor development, and immune system activation. In this study, six novel derivatives of aspartic acid carboxamides (11a-f) were synthesized using phenylboronic acid as a coupling agent of benzene sulphonyl chloride and aspartic acid. Biophysical characterization of the synthesized amides employed the FTIR, ¹ H, and ¹³ C NMR spectroscopic techniques. The amide derivatives exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging property with IC ₅₀ values of 159.96, 51.94, 99.74, 91.99, and 114.17 µg/ml for the synthesized compounds 11a, 11b, 11c, 11d, 11e, and 11f, compared to 13.38 µg/ml of ascorbic acid standard. The peroxidase modulatory activity assay showed that compounds 11a and b had the maximum peroxidase activation potential in a concentration-dependent manner. However, 11c, d, e, and f inhibited peroxidase activity. Molecular docking studies confirmed that compounds 11a and b possess high affinity with the lowest binding energy of -9.5 and − 10.0 kcal/mol, respectively. The ADMET analysis revealed that the synthesized compounds obeyed the Lipinski rule of five as potential drug candidates. Therefore, these compounds could be employed as potential drug candidates for combating oxidative stress, inflammation, and auto-oxidation of biological membranes for therapeutic intervention.