Multi-target macrocycles: pyrogallol derivatives to control multiple pathological factors associated with Alzheimer’s disease DOI Creative Commons

Jimin Kwak,

Yelim Yi, Seongmin Park

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Designing multi-target chemical tools is a vital approach to understanding the pathology of Alzheimer's disease (AD), which involves complex network pathological factors, such as free organic radicals, amyloid-β (Aβ), and metal-bound Aβ (metal-Aβ). The pyrogallol moiety, known for its ability lower redox potentials interact with both metal ions, presents promising framework this molecular design. Here we show how simple structural variations can be used enhance scavenge radicals regulate aggregation metal-free metal-Aβ. By incorporating multiple pyrogllol units into macrocyclic scaffold

Language: Английский

Reversing Signs of Parkinsonism in a Cell Model Using Mitochondria-Targeted Organoiridium Catalysis DOI

Rahul D. Jana,

Hieu D. Nguyen,

Guangjie Yan

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

We report the application of organoiridium complexes as catalytic agents for detoxification biogenic reactive aldehyde species (RASP), which are implicated in pathogenesis neurodegenerative disorders. show that Ir functionalized with phosphonium cations localize selectively mitochondria and have better cellular retention compared to their parent species. In a cell model Parkinsonism, mitochondria-targeted iridium catalysts exhibited superior protecting abilities longer-lasting effects (up 6 d) than conventional RASP scavengers, failed be effective beyond 24 h. Our biological assays indicate treatment compounds led reduction oxygen levels while partially preserving native mitochondrial membrane potential NAD

Language: Английский

Citations

0
Role of Amyloidogenic and Non‐Amyloidogenic Protein Spaces in Neurodegenerative Diseases and their Mitigation Using Theranostic Agents DOI

Kapali Suri,

Madhu Ramesh,

Mansi Bhandari

et al.

ChemBioChem, Journal Year: 2024, Volume and Issue: 25(13)

Published: April 26, 2024

Abstract Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of which are associated with the accumulation amyloid fibrils or plaques in brain leading progressive loss neuronal functions. Alzheimer's disease is one major NDD responsible for 60–80 % all dementia cases. Currently, there no curative disease‐reversing/modifying molecules many NDDs except few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa treat disease‐associated symptoms. Similarly, very FDA‐approved tracers flortaucipir (Tauvid) tau fibril imaging florbetaben (Neuraceq), flutemetamol (Vizamyl), florbetapir (Amyvid) available diagnosis. Recent advances cryogenic electron microscopy reported distinctly different microstructures tauopathies highlighting possibility develop tauopathy‐specific agents therapeutics. In addition, it important identify proteins that development progression know about their 3D structure various diagnostics, therapeutics theranostic agents. The current article discusses detail non‐amyloid along structural insights. We comprehensively discussed novel implications pathology. we document emerging chemical compounds developed diagnosis therapy special emphasis on better management NDDs.

Language: Английский

Citations

2
Piano-stool metal complexes as inhibitors of amyloid-β aggregation in vitro and in vivo DOI Creative Commons
Gloria Vigueras, Raimon Sabaté, Leoní A. Barrios

et al.

Inorganic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(18), P. 6089 - 6102

Published: Jan. 1, 2024

Half-sandwich arene osmium( ii ) complex 2 can inhibit the amyloid-β aggregation in vitro and vivo using a Caenorhabditis elegans animal model of Alzheimer's disease.

Language: Английский

Citations

2
Synthesis of Symmetrical and Unsymmetrical Tetrahydroxybiphenyls and their Evaluation as Amyloid-β Aggregation Inhibitors DOI Creative Commons
Sarah L. Wicks,

Jake A. Roberts,

Matthew J. Hurtt

et al.

Letters in Organic Chemistry, Journal Year: 2024, Volume and Issue: 21(11), P. 964 - 972

Published: April 2, 2024

Abstract: Our group recently reported that the polyhydroxy aromatic compound 3,3′,4,4′- biphenyltetrol (2a) is a successful inhibitor of amyloid-β peptide (Aβ) aggregation, decreasing Aβ aggregation by 50 % when present in equimolar concentrations. In study, several additional biphenyltetrols were prepared and examined for their vitro activity against to investigate effect relative positions hydrogen-bond donors on process. Congo red spectral shift assays demonstrated that, eight (8) compounds prepared, three (3) successfully inhibited association monomers, two symmetrical isomers, 2,2′,5,5′-biphenyltetrol (2c), 2,2′,3,3′-biphenyltetrol (2d), along with one unsymmetrical isomer, 2,3′,4′,5-biphenyltetrol (2g). These results, previously results 2a, strongly suggest hydroxyl position affects ability bind assemblies, thus impacting inhibitory efficacy.

Language: Английский

Citations

0
Piperonal protects neuron-like and retinalpigment epithelial (RPE) cells from oxidative stress and apoptosis through inhibition of α-synuclein aggregation DOI Creative Commons
Meiqi Wang, Tao Yang, Weiying Chen

et al.

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(10), P. 105982 - 105982

Published: Aug. 29, 2024

Language: Английский

Citations

0
Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly DOI Creative Commons
Mona Kalmouni, Yujeong Oh, Waël Alata

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1443 - 1443

Published: Nov. 12, 2024

Peptides possess a number of pharmacologically desirable properties, including greater chemical diversity than other biomolecule classes and the ability to selectively bind specific targets with high potency, as well biocompatibility, biodegradability, ease low cost production. Consequently, there has been considerable interest in developing peptide-based therapeutics, amyloid inhibitors. However, major hindrance successful therapeutic application peptides is their poor delivery target tissues, cells or subcellular organelles. To overcome these issues, recent efforts have focused on engineering cell-penetrating peptide (CPP) antagonists amyloidogenesis, which combine attractive intrinsic properties potent effects (i.e., inhibition formation associated cytotoxicity) highly efficient (to tissue, cells, organelles). This review highlights some promising CPP constructs designed aggregation diverse range disorders, Alzheimer's disease, transmissible spongiform encephalopathies (or prion diseases), Parkinson's cancer.

Language: Английский

Citations

0
Multi-target macrocycles: pyrogallol derivatives to control multiple pathological factors associated with Alzheimer’s disease DOI Creative Commons

Jimin Kwak,

Yelim Yi, Seongmin Park

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 3, 2024

Designing multi-target chemical tools is a vital approach to understanding the pathology of Alzheimer's disease (AD), which involves complex network pathological factors, such as free organic radicals, amyloid-β (Aβ), and metal-bound Aβ (metal-Aβ). The pyrogallol moiety, known for its ability lower redox potentials interact with both metal ions, presents promising framework this molecular design. Here we show how simple structural variations can be used enhance scavenge radicals regulate aggregation metal-free metal-Aβ. By incorporating multiple pyrogllol units into macrocyclic scaffold

Language: Английский

Citations

0