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

Abstract

Worldwide, Alzheimer's disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ₄₂) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

Keywords: Alzheimer’sdisease; curcumin analogues; derivatives; diagnosis; hybrids; therapy.

Figure 1

Inhibitors of amyloid-β aggregation.

Figure 2

Inhibitors of amyloid-β aggregation.

Figure 3

Inhibitors of amyloid-β aggregation.

Figure 4

Inhibitors of amyloid-β aggregation.

Figure 5

Mixed curcuminoids having anti-amyloid properties.

Figure 6

Mixed curcuminoids having antioxidant properties.

Figure 7

Anti-inflammatory inhibitors.

Figure 8

Anti-inflammatory inhibitors.

Figure 9

Antioxidant inhibitors.

Figure 10

Antioxidant inhibitors.

Figure 11

Antioxidant inhibitors.

Figure 12

Antioxidant inhibitor.

Figure 13

Antioxidant inhibitor.

Figure 14

Antioxidant inhibitor.

Figure 15

AChE inhibitors.

Figure 16

Curcumin-based hybrids.

Figure 17

NIRF probe (1) with “turn-on” fluorescence.

Figure 18

Therapeutic targets of curcumin analogues, derivatives, and hybrids in AD.