Curcumin as Scaffold for Drug Discovery against Neurodegenerative Diseases

Cascio, Filippa Lo; Marzullo, Paola; Kayed, Rakez; Piccionello, Antonio Palumbo

doi:10.3390/biomedicines9020173

Cited by 18 publications

(12 citation statements)

References 141 publications

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“…A new series of curcumin-coumarin hybrid analogues 11-18 were synthesized in low yield starting from 2 ,2 -diphenyl-1,3-dioxol[h]coumarin-3-carbaldehyde (5), or 2 ,2 -diphenyl-1,3-dioxol[g]coumarin-3-carbaldehyde (9), and the corresponding tris (methoxymethoxy)benzaldehyde 10a-d. Synthesized derivatives did not reach a potential as a multitarget drug.…”

Section: Discussionmentioning

confidence: 99%

“…With the same objective and also to improve its activity, in recent years, many compounds derived from curcumin have been designed and synthesized. Some of them have shown anti-amyloidogenic activity, inhibitory of the formation of tau, as well as anti-neuroinflammatory, antioxidant, and inhibitory of acetylcholinesterase (AChE) [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders

et al. 2021

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Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin–coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11–18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders

et al. 2021

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“…Notably, the design of stable monomeric TDP-43 variants (i.e., double mutant S333D/S342D) with the ability to be purified as stable monomers enabled the identification of small molecules capable of stabilizing the protein's native state and preventing aggregation (Yang et al, 2023). Compounds with the ability to modulate the aggregation pathways and toxicity of amyloidogenic proteins such as MB and curcumin (Lo Cascio et al, 2021;Gureev et al, 2022) also prevent Frontiers in Molecular Biosciences frontiersin.org aggregation. MB reduces cytoplasmic TDP-43 inclusions in cells (Yamashita et al, 2009) and suppresses mutant TDP-43-mediated toxicity in C. elegans and zebrafish ALS (Vaccaro et al, 2012;Vaccaro et al, 2013) but was ineffective in reducing disease symptoms and cytoplasmic accumulation of TDP-43 in transgenic TDP-43 (G348C) mice (Audet et al, 2012).…”

Section: Molecules Targeting Tdp-43 Misfolding and Aggregationmentioning

confidence: 99%

Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS

Tsekrekou,

Giannakou,

Papanikolopoulou

et al. 2024

Front. Mol. Biosci.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with severe socio-economic impact. A hallmark of ALS pathology is the presence of aberrant cytoplasmic inclusions composed of misfolded and aggregated proteins, including both wild-type and mutant forms. This review highlights the critical role of misfolded protein species in ALS pathogenesis, particularly focusing on Cu/Zn superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP-43), and emphasizes the urgent need for innovative therapeutic strategies targeting these misfolded proteins directly. Despite significant advancements in understanding ALS mechanisms, the disease remains incurable, with current treatments offering limited clinical benefits. Through a comprehensive analysis, the review focuses on the direct modulation of the misfolded proteins and presents recent discoveries in small molecules and peptides that inhibit SOD1 and TDP-43 aggregation, underscoring their potential as effective treatments to modify disease progression and improve clinical outcomes.

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“…Curcumin has been shown to significantly enhance cognitive dysfunction and motor function in the central nervous system ( Lo Cascio et al, 2021 ). Improvements in cognition are facilitated by reduced neuronal loss and hippocampal synaptic repair.…”

Section: Neuroprotective Functions and Mechanisms Of Curcuminmentioning

confidence: 99%

Pharmacological intervention of curcumin via the NLRP3 inflammasome in ischemic stroke

Du,

Amin,

et al. 2023

Front. Pharmacol.

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Ischemic-induced neuronal injury arises due to low oxygen/nutrient levels and an inflammatory response that exacerbates neuronal loss. NOD-like receptor family pyrin domain-containing 3 (NLRP3) is an important regulator of inflammation after ischemic stroke, with its inhibition being involved in nerve regeneration. Curcumin, a main active ingredient in Chinese herbs, plays a positive role in neuronal repair and neuroprotection by regulating the NLRP3 signaling pathway. Nevertheless, the signaling mechanisms relating to how curcumin regulates NLRP3 inflammasome in inflammation and neural restoration following ischemic stroke are unknown. In this report, we summarize the main biological functions of the NLRP3 inflammasome along with the neuroprotective effects and underlying mechanisms of curcumin via impairment of the NLRP3 pathway in ischemic brain injury. We also discuss the role of medicinal interventions that target the NLRP3 and potential pathways, as well as possible directions for curcumin therapy to penetrate the blood–brain barrier (BBB) and hinder inflammation in ischemic stroke. This report conclusively demonstrates that curcumin has neuroprotective properties that inhibit inflammation and prevent nerve cell loss, thereby delaying the progression of ischemic brain damage.

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Curcumin as Scaffold for Drug Discovery against Neurodegenerative Diseases

Cited by 18 publications

References 141 publications

Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders

Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders

Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS

Pharmacological intervention of curcumin via the NLRP3 inflammasome in ischemic stroke

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