Regioselective synthesis of cyclodextrin mono-substituted conjugates of non-steroidal anti-inflammatory drugs at C-2 secondary hydroxyl by protease in non-aqueous media

Three 2-O-mono-substituted β-cyclodextrin (β-CD) conjugates of indomethacin, ketoprofen and etodolac were synthesized by enzymatic methods. Three β-cyclodextrin (β-CD) conjugates of non-steroidal anti-inflammatory drugs were synthesized by enzymatic methods. Transesterification of β-CD with vinyl ester of indomethacin, ketoprofen and etodolac was performed by the catalysis of alkaline protease from Bacillus subtilis in anhydrous DMF for 3days. The drug molecules were selectively conjugated onto one of the secondary hydroxyl groups of β-CD through ester-linkage to improve their poor water solubility and absorption characteristics. The products were characterized by ESI-MS, 1H NMR and 13C NMR. The structures of products with monoacylation occurring at the C-2 secondary hydroxyl groups of β-CD were confirmed.