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 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 3 days. 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.

Three 2-O-mono-substituted β-cyclodextrin (β-CD) conjugates of indomethacin, ketoprofen and etodolac were synthesized by enzymatic methods.Figure optionsDownload as PowerPoint slide