Binding behavior of ibuprofen-based ionic liquids with bovine serum albumin: Thermodynamic and molecular modeling studies

Abstract

• Nine ibuprofen-based ionic liquids containing cations amino acid alkyl esters [AAOR] were synthesized and characterized. • The [AAOR][Ibu] are not toxic against mouse fibroblasts and keratinocytes. • Ibu-ILs bind spontaneously to bovine serum albumin with moderate affinities (Ka 1–3.7 × 10 5 L/mol) at 25 °C. • Depending on their structures, [AAOR] showed differences at the preferred binding site of bovine serum albumin. Ionic liquids based on active-pharmaceutical ingredients are an attractive alternative to classical drugs because they are able to overcome problems with drug solubility and polymorphism, hence bioavailability and as well as to propose different routes of administration and/or improve the pharmacokinetics of the drug. In this manuscript, we report the synthesis of nine amino acid alkyl esters of ibuprofen [AAOR][Ibu]. The estimated half-maximum inhibitory constants toward murine embryotic fibroblasts and human dermal keratinocytes are in the millimolar range, which makes them practically not toxic. The conversion of ibuprofen into ionic liquids does not affect the binding affinity of ibuprofen to bovine serum albumin (BSA). Molecular modeling studies have shown that bulky cations such as L-PheOEt and L-PheOPr are able to bind effectively in three different BSA binding sites. On the other hand, smaller cations preferably bind to Sudhow’s site I, the same that binds ibuprofen.