Pharmacokinetic Studies of Curcumin Based Pyrazoline MAO Inhibitors

Background: Curcumin is a natural phenolic compound obtained from Curcuma longa, with proven human monoamine oxidase (MAO) inhibitory activity, but due to its poor oral bioavailability, blood-brain barrier permeability and extensive metabolism in the liver, it has never been recognized as a drug candidate. Purpose: In this study, the structure-based-drug design (SBDD) was adopted to incorporate the structural features of Curcumin with an aim to improve drug permeability and metabolic stability. Method: A series of ferulic amides (half portion of curcumin) (1-3) and curcumin based pyrazolinescompounds (4-6) were designed and Curcumintested for their membrane permeability and liver microsomal metabolic stability in a various animal in an in-vitro assay system. Conclusion: All the designed compounds showed a significant enhancement in permeability and metabolic stability is achieved through chemical modification.