In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes

Abstract

Curcumin and its derivatives have attracted great interest in the prevention and treatment of Alzheimer's disease, thanks both to the ability to hinder the formation of amyloid-beta (Aβ) aggregates and the ability to bind Cu (II) ion. In this article, we explore the ability of curcumin derivatives of K2T series to affect amyloid Aβ aggregation. These derivatives were obtained by introducing the t-butyl ester group through a methylenic spacer on the central carbon atom of the β-diketo moiety of curcumin frame. The studied curcuminoids were demonstrated to inhibit Aβ fibrillization at substoichiometric concentrations with IC value near that of curcumin. In addition, the antioxidant properties and DNA interaction of their Cu(II) complexes is evaluated. The structure of Cu(II)-K2T31 complex is also proposed on the basis of DFT calculation.

Cytotoxicity Evaluation of Turmeric Extract Incorporated Oil-in-Water Nanoemulsion

“…Turmeric extract powder (TEP) used in this study for the production of curcumin nanoemulsion, is a mixture containing a number of commercially available vegetable supplements [ 5 ]. Among them, the pharmacological activity of curcumin, an index substance of turmeric, has been reported through many studies [ 6 , 7 , 8 ]. However, curcumin, a yellow hydrophobic polyphenolic component extracted from turmeric has limited applications due to poor solubility and toxicity at high concentrations [ 9 , 10 , 11 ].…”

Synthesis and Structure Activity Relationship of Pyridazine-Based Inhibitors for Elucidating the Mechanism of Amyloid Inhibition

“…However, when the hydroxyl group is in para position, the inhibitory effect is reduced. Since anti-amyloid properties of several compounds have been linked to their antioxidant effects, bond dissociation energy (BDE) has been used as a parameter to compare antioxidant potency. − Interestingly, when BDE was calculated for both Py-1 and Py-2, the meta-substituted compound (Py-1) displayed a lower BDE (Figure S18); therefore, Py-1 can potentially act as an antioxidant more effectively than Py-2. Interestingly, when the hydroxyl groups were completely removed (as in Py-4), amyloid inhibition was significantly reduced; however, the amyloid formation was not completely prevented most likely due to the presence of pyridazine ring and hydrogen bonding between the amino group of the inhibitor and the protein (Figure B).…”

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

“…Ferrari et al [40] proposed that AB31 is the best candidate for the development of new curcumin-based analogues to treat AD, due to its multifaced intrinsic characteristics which include: (i) it is able to inhibit Aβ 1-40 aggregation; (ii) it seems that it is tightly bound to Cu(II) giving more stable complexes with respect to curcumin, reducing metal concentration in the free form and, consequently, limiting Aβ 1-40 aggregation; and also (iii) AB31 is more stable than curcumin in physiological conditions, suggesting higher bioavailability. AB31 was derived by the introduction of a t-butyl ester group attached to a methylenic linker on the the β-diketo moiety of curcumin frame ( Figure 2 and Table 1).…”

“…Therefore, the complexes of gallium(III) look very promising as superoxidescavengers suggesting their possible use as SOD mimics (Figure 2 and Table 2). Additional research [40] revealed that the co-ordination of copper ion by the keto-enolic group has a protecting role since the involvement of the keto-enolic moiety in the radical delocalizationis prevented. Among the different proposed reaction mechanisms, the involvement of the keto-enolic group in stabilizing the formed radical through delocalization was also reported.…”