SEMI-SYNTHESIS OF (-)-HINOKININ AND (-)-O-BENZYL CUBEBIN FROM (-)-CUBEBIN AND THEIR ANTI-INFLAMMATORY MECHANISM OF ACTION

Abstract

Purpose: Dibenzylbutyrolactone lignans have a broad spectrum of biological activities such as antitumor, antiviral, anti-inflammatory, inhibition of platelet activating factor, and trypanocidal, among others. Among these lignans, (-)-cubebin, isolated from Zanthoxyllum naranjillo and Piper cubeba , so the aim of this work was to evaluated the anti-inflammatory activity. Using (-)-cubebin as starting material, we have obtained the derivatives (-)-hinokinin and (-)-O-benzyl cubebin, which were potentially more efficacious than (-)-cubebin. Methods: Using (-)-cubebin as starting material, we have obtained the derivatives (-)-hinokinin and (-)-O-benzyl cubebin, which were potentially more efficacious than (-)-cubebin which was evaluated using paw edema method. Results: Using the paw edema as experimental model and various chemical mediators, such as prostaglandins and dextran, it was observed that both derivatives were more active in comparison with positive control (Indomethacin), being (-)-O-benzyl-cubebin more effective by reducing the edema induced by prostaglandin by 66%, while (-)-hinokinin inhibited 59.2%. On the other hand, the paw edema induced by dextran was not significantly reduced by (-)-hinokinin and (-)-O-benzyl-cubebin, which inhibit the edema formation by 3.52% and 18.35%, respectively, and for the positive control (cyproheptadine) it was 56%.