<i>CAL-B</i> promoted amidation of (<i>S</i>)-ibuprofen: Mechanistic study and <i>in vitro versus in silico</i> evaluation of the anti-inflammatory activity

An efficient preparation of (<i>S</i>)-<i>N</i>-benzyl-2-(4-isobutylphenyl)propanamide (<i>S</i>)-AMD <i>via</i> direct condensation of (<i>S</i>)-IBU and benzylamine catalyzed, by the immobilized <i>Candida antarctica</i> lipase fraction-B, is described. A mechanistic study of the enzymatic amidation is performed, aided by molecular docking. This study is coupled with the evaluation of the inhibitory potency of the prodrug amide through docking simulations into the active sites of the human <i>h</i>COX-1 (6Y3C) and <i>h</i>COX-2 (5KIR) enzymes. Furthermore, the potential anti-inflammatory activity of the synthesized (<i>S</i>)-AMD is evaluated using an albumin denaturation inhibition assay. <i>In silico</i> calculations of pharmacokinetic properties, toxicity and bioactivity are also reported. Based on the findings of this study, it has been shown that the prodrug presents better anti-inflammatory properties than the parent drug, (<i>S</i>)-Ibuprofen, and may be considered a potent selective COX-2 inhibitor.