Synthesis and evaluation of curcumin derivatives toward an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1

Konno, Hiroyuki; Endo, Hitoshi; Ise, Satomi; Miyazaki, Keiki; Aoki, Hideo; Sanjoh, Akira; Kobayashi, Kazuya; Hattori, Yoshiyuki; Akaji, Kenichi

doi:10.1016/j.bmcl.2013.11.039

Cited by 35 publications

(36 citation statements)

References 19 publications

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“…Konno and colleagues (2014) [63] studied the impact of a new non-peptidyl inhibitor of beta-site amyloid precursor protein cleaving enzyme 1 in AD. They focused on the curcumin framework, two phenolic groups combined with an sp2 carbon spacer for low-molecular and high lipophilicity.…”

Section: Curcumin and Its Multifunctional Role In Human Healthmentioning

confidence: 99%

“…The structure-activity relationship study of curcumin derivatives is described. Their results indicate that phenolic hydroxyl groups and an alkenyl spacer are important structural factors for the inhibition of beta-site amyloid precursor protein cleaving enzyme 1 and, furthermore, non-competitive inhibition of enzyme activity is anticipated from an inhibitory kinetics experiment and docking simulation [63]. …”

Section: Curcumin and Its Multifunctional Role In Human Healthmentioning

confidence: 99%

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Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Reddy

Mańczak

Yin

et al. 2018

JAD

285

138

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The purpose of our article is to assess the current understanding of Indian spice ‘Curcumin’ against amyloid-β (Aβ)-induced toxicity in Alzheimer’s disease (AD) pathogenesis. Natural products, such as ginger, curcumin and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, anti-oxidant, anti-arthritis, pro-healing and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells and protect neurons from various toxic insults of aging and amyloid-β in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin’s bioavailability and urgent need for new formulation to increase its brain levels to treat patients with AD.

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Section: Curcumin and Its Multifunctional Role In Human Healthmentioning

confidence: 99%

Section: Curcumin and Its Multifunctional Role In Human Healthmentioning

confidence: 99%

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Reddy

Mańczak

Yin

et al. 2018

JAD

285

138

View full text Add to dashboard Cite

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“…Due to its wide range of pharmacological activities, various curcumin analogs (Figure ) have been synthesized and evaluated. The curcumin analogs exhibit inhibitory activities against AChE, Tau, βA 1‐42 aggregation, β‐secretase cleaving enzyme (BACE1) and also some of them have the ability to scavenge the free radicals and also chelates metal ions (Chen et al, ; Fang, Gou, Liu, Cao, & Cheng, ; Konno et al, ; Okuda et al, ; Yan et al, ; Yanagisawa, Taguchi, et al, ).…”

Section: Curcuminmentioning

confidence: 99%

“…F I G U R E 1 1 Curcumin based multitarget molecules as anti-Alzheimer agents 2011 ;Fang, Gou, Liu, Cao, & Cheng, 2014;Konno et al, 2014;Okuda et al, 2016;Yan et al, 2017;.…”

Section: Curcuminmentioning

confidence: 99%

Natural products and their derivatives as multifunctional ligands against Alzheimer's disease

Patil

Thakur

Sharma

et al. 2019

Drug Development Research

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Alzheimer's disease (AD), a complex neurodegenerative disorder causing multiple cellular changes including impaired cholinergic system, beta‐amyloid (βA) aggregation, tau hyperphosphorylation, metal dyshomeostasis, neuroinflammation, and many other pathways are involved in the pathogenesis of the disease. However, the exact cause of the disease is not known. Natural products such as flavonoids, alkaloids, resveratrol, and curcumin have multifunctional properties, and have drawn the attention of the researchers because these molecules are capable of interacting concurrently with the multiple targets of AD. Therefore, natural products and their derivatives with proven efficacy could be used in the management of the neurodegenerative disorders. This review focuses on the natural product based multitarget directed ligands like tacrine‐coumarin, tacrine‐huperzine A, harmine‐isoxazoline, berberine‐thiophenyl, galantamine‐indole, pyridoxine‐resveratrol, donepezil‐curcumin and their mode of action.

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“…All amyloid fibrils have characteristic elongated fibrillar morphology with a ß‐sheet‐rich structure. The formation of well‐ordered fibrillar protein deposits is common to a large group of amyloid associated disorders such as AD, PD, prion diseases, HD, and familial amyloidosis .…”

Section: General Introduction To Protein Misfolding and Aggregation/amentioning

confidence: 99%

Underlying mechanisms and chemical/biochemical therapeutic approaches to ameliorate protein misfolding neurodegenerative diseases

2016

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Protein misfolding and inclusion body formations are common events in neurodegenerative diseases characterized by deposition of misfolded proteins inside or outside of neurons, and are commonly referred to as "protein misfolding neurodegenerative diseases" (PMNDs). These phenotypically diverse but biochemically similar aggregates suggest a highly conserved molecular mechanism of pathogenesis. These challenges are magnified by presence of mutations that render individual proteins subject to misfolding and/or aggregation. Cell proteostasis network and molecular chaperoning are maintaining cell proteome to preserve the protein folding, refolding, oligomerization, or disaggregation, and play formidable tasks to maintain the health of organism in the face of developmental changes, environmental insults, and rigors of aging. Maintenance of cell proteome requires the orchestration of major pathways of the cellular proteostasis network (heat shock response (HSR) in the cytosol and the unfolded protein response (UPR) in the endoplasmic reticulum). Proteostasis responses culminate in transcriptional and post-transcriptional programs that up-regulate the homeostatic mechanisms. Proteostasis is strongly influenced by the general properties of individual proteins for folding, misfolding, and aggregation. We examine a growing body of evidence establishing that when cellular proteostasis goes awry, it can be reestablished by deliberate chemical and biological interventions. We first try to introduce some new chemical approaches to prevent the misfolding or aggregation of specific proteins via direct binding interactions. We then start with approaches that employ chemicals or biological agents to enhance the general capacity of the proteostasis network. We finish with evidence that synergy is achieved with the combination of mechanistically distinct approaches to reestablish organ proteostasis. © 2016 BioFactors, 43(6):737-759, 2017.

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Synthesis and evaluation of curcumin derivatives toward an inhibitor of beta-site amyloid precursor protein cleaving enzyme 1

Cited by 35 publications

References 19 publications

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Natural products and their derivatives as multifunctional ligands against Alzheimer's disease

Underlying mechanisms and chemical/biochemical therapeutic approaches to ameliorate protein misfolding neurodegenerative diseases

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