Synthesis of fatty acid derivatives of curcumin as new lipophilic prodrugs

Today, the use of lipophilic prodrugs is one of the important issues in drug delivery. Lipophilic prodrugs can have an important role in improving bioavailability, passing biological membranes, Facilitating drug transfer, targeting drugs and treatment of cancer. The ultimate goal in prodrugs design is to overcome the different limitations of drugs, and access to pharmacokinetics of drugs. Curcumin, which is derived from Curcuma longa, has a wide range of therapeutic activities, such as anti-tumor activity, antioxidant. The purpose of this study was to design and produce lipophilic curcumin prodrug based on Oleic acid. A mixture of Oleic acid, DCC and catalytic amount of 4-dimethylaminopyridine (DMAP) in ethanol as a solvent, then (0.5 mmol) of curcumin was added at room temperature under magnetic stirring conditions until the reaction was complete. Eventually, the N, N–dicyclohexylurea was filtered off and the solvent was removed under reduced pressure to give the product which was chromatographed over a column of silica gel using methanol as eluent. In this study, a lipophilic curcumin prodrug was synthesized during the esterification reaction between the carboxylic acid of Oleic acid and the hydroxyl groups of curcumin. The synthesized prodrug was characterized using IR, 1H-NMR and 13C-NMR spectroscopy. An appropriate method for esterification reactions of curcumin and Oleic acid was developed. Derivatives lipophilic prodrug curcumin were successfully synthesized in order to improve the bioavailability and also characterized the compound structures [1-3].