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.

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

“…Curcumin, a phenolic compound, is also known as diferuloylmethane with chemical name of (1E, 6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) ( Figure 1 ) ( Baldi et al, 2020 ; Chainoglou and Hadjipavlou-Litina, 2020 ; Salehi et al, 2020a ; Stohs et al, 2020 ). This biologically active compound occurs in high amounts in rhizome and roots of turmeric plant ( Curcuma longa ) ( Hesari et al, 2019 ).…”

Curcumin, a Natural Antimicrobial Agent with Strain-Specific Activity

“…This natural molecule also exhibits antibacterial, antifungal, antiviral, antiprotozoal, and antiparasitic properties [ 12 , 13 , 14 ]. Clinical trials have demonstrated the therapeutic benefits of curcumin supplementation in patients with inflammatory diseases (arthritis, inflammatory bowel disease, peptic ulcer, and H. pylori infection), metabolic syndrome, neurodegenerative diseases, and cancer, including colorectal, pancreatic, and breast cancers [ 11 , 15 , 16 , 17 , 18 ]. Due to the wide range of biological activities of curcumin and its pleiotropic therapeutic potential, this substance has been of great interest to researchers.…”

Pyrazole Scaffold Synthesis, Functionalization, and Applications in Alzheimer’s Disease and Parkinson’s Disease Treatment (2011–2020)

“…Curcumin ( 177 ), a natural phenolic compound found in the rhizome of Curcuma longa, has been used to treat various ailments in India for centuries. Structural modifications of curcumin to improve its instability and bioavailability have been an attractive strategy in new drug discovery [ 95 , 96 ]; several pyrazole-containing curcumin derivatives have showed potency for AD treatment [ 97 ]. CNB-001 ( 178 ), a pyrazole derivative of curcumin, was initially found to have broad neuroprotective activity [ 98 , 99 ].…”