Chapter 7 - Curcumin, a Multitarget Phytochemical: Challenges and Perspectives

Abstract

Abstract Curcumin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-Dione] is a phytochemical obtained from the dried rhizomes of Curcuma longa L. This yellow pigment is the main constituent of turmeric powder, a spice widely used in Southeast Asia. Curcumin has been used for centuries in traditional Indian and Chinese medicine, particularly as an anti-inflammatory agent. In recent years, several studies have shown that curcumin has a variety of biological and pharmacological activities, such as anticarcinogenic, antioxidant, immunomodulator, antiangiogenic and also in chemoprevention. However, preclinical and clinical studies have found that the potentially beneficial effects of curcumin on various disease preventions and treatments are limited by its poor pharmacokinetic properties due to its instability under physiological conditions, which prevents its therapeutic utility. The major structural issue of curcumin is the presence of the active methylene group and β-diketone moiety that causes instability of curcumin under physiological conditions, poor absorption, and fast metabolism. Therefore different synthetic approaches have been intensively studied in order to develop curcumin analogs with improved biological properties and better stability. Another strategy to overcome the poor bioavailability is the direct loading of the curcumin in nanostructured systems. Computational approaches investigating the curcumin and its derivatives at a molecular level gives a detailed interpretation of ligand-target interaction and provides insights for the development of more effective and stable compounds. In this chapter, we include a review of the application of docking, molecular dynamics, pharmacophore, and QSAR models in the development of improved curcumin derivatives, and also it was discussed the molecular recognition against its main targets for antitumor, anti-HIV, antioxidant, and antifungal biological activities. Overall, we present an analysis of curcumin and its derivatives, the main synthetic and computational approaches applied for curcumin modification ligand-target molecular recognition and the improvement of its pharmacological effects by the development of nanoparticles.