Pharmacokinetic Studies of Curcumin Based Pyrazoline MAO Inhibitors

Abstract

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.

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Keywords

Structure-based-drug design, Curcumin based Pyrazoline analogues, Ferulic acid amides, MDCK-II permeability studies, Liver microsomal metabolic stability studies

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