A study of conjugate addition of curcumin and chalcone derivatives

Curcumin is one of the promising herbal-based drugs. It has been shown to have antioxidant,antibacterial, anti-angiogenic and other activities. As curcumin's derivative, chalcone shares similar functions. Both of these two compounds have alpha,beta-unsaturated carbonyl structures(enone), which is a typical 1,4-conjugate addition (Michael addition) acceptor. Glutathione is an endogenous tripeptide, whose sulfhydral group is a typical nucleophilic agent. In this case, the derivatives of curcumin and chalcone may be reduced by glutathione and their pharmacological functions would be changed. The study focused on how to use quantum chemistry tools and transition state theory to access to the conjugate addition of alpha,beta-unsaturated carbonyl compounds. Besides, the reductions of the derivatives of chalcone were also studied. The characteristics of the reactions were obtained by analyzing geometries and energy profiles of the simplified reactions, as well as the influence of functional groups on derivatives in this type of reaction. This study may be generally useful for the scientific community for two fundamental reasons: (a) to provide general strategies to enhance or retard drugs from reacting with glutathione, and (b) to provide insight into computational methods that are able to help design potential lead candidates