Synthesis, biological activity, X-ray crystallographic, DFT calculations and molecular dynamics simulation studies of 2-phenylthiazole-1,3,5-triazine derivatives as potential cholinesterase inhibitors

Journal of Molecular Structure, Год журнала: 2024, Номер 1309, С. 138203 - 138203

Опубликована: Апрель 5, 2024

Язык: Английский

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Antioxidants in Anti-Alzheimer's Disease Drug Discovery

Ageing Research Reviews, Год журнала: 2025, Номер 107, С. 102707 - 102707

Опубликована: Фев. 27, 2025

Язык: Английский

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Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer’s disease

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2024, Номер 39(1)

Опубликована: Фев. 16, 2024

Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer's disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives evaluated their activities against cholinesterases neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC50 = 4.68 nM; huBuChE 9.12 nM) anti-neuroinflammatory (NO inhibition 28.82% at 10 μM, comparable to hydrocortisone). Enzyme kinetic docking studies confirmed was a mix-type inhibitor. Additionally, displayed favourable drug-likeness properties in silico prediction, high BBB permeability the PAMPA-BBB assay. Compound had good safety vivo verified by an acute toxicity assay (LD50 > 1000 mg/kg). Most importantly, effectively mitigated cognitive memory impairments scopolamine-induced mouse model, showing effects Rivastigmine. Therefore, envisioned that could serve lead treating AD.

Язык: Английский

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A novel carbamate-based hybrid derivative with anti-neuroinflammatory properties as a selective butyrylcholinesterase inhibitor for Alzheimer's disease therapy

Bioorganic Chemistry, Год журнала: 2025, Номер 161, С. 108551 - 108551

Опубликована: Май 4, 2025

Язык: Английский

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Oxidovanadium(IV) Porphyrin-Imidazole Complex-Catalyzed One-Pot, Three-Component Green Synthesis of Biologically Active Pyrano[2,3-d]pyrimidine and 4H-Chromene Heterocycles

Inorganic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Май 12, 2025

A β-functionalized porphyrin ligand {H2TPP(Phen)}, has been synthesized and subsequently employed as a dibasic tetradentate in synthesizing its vanadyl complex 2-(1H-imidazo[4,5-f][1,10]phenanthroline-2-yl)-5,10,15,20-tetraphenylporphyrinatooxido-vanadium(IV)[VIVOTPP(Phen)] (1). Comprehensive characterization of the {H2TPP(Phen)} vanadyl(IV) (1) was achieved through various analytical spectroscopic techniques, including NMR, ultraviolet-visible (UV-vis), EPR, MALDI-TOF mass spectrometry elemental analysis. Electrochemical studies indicated that free base tends to four successive reduction peaks two oxidation observed cyclic voltammetry. In contrast, metalated [VIVOTPP(Phen)] displayed reversible reductions peaks. The vanadyl(IV)-porphyrin further an efficient reusable catalyst environmentally friendly, one-pot, three-component synthesis biologically clinically relevant pyrano[2,3-d]pyrimidine (Ca-Ch, Da-Dg) 4H-chromene (Ga-Gj, Ha-Hj) heterocycles. Based on current literature regarding multicomponent reactions, distinct plausible mechanistic pathways are postulated for these transformations. detailed investigation, isolation intermediates stepwise reaction analysis, revealed type 1,3-dicarbonyl compound used is pivotal determining operative pathway reactions. catalytic protocol developed heterocycles presents several advantages over existing methodologies, use eco-friendly solvent (ethanol), high product yields (up 97%), shorter time scale (30 min), turnover frequency (TOF) values 14.7 min-1), excellent reusability five cycles.

Язык: Английский

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Discovery of novel deoxyvasicinone derivatives with benzenesulfonamide substituents as multifunctional agents against Alzheimer's disease

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 264, С. 116013 - 116013

Опубликована: Ноя. 30, 2023

Язык: Английский

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Compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one downregulation of Galectin-3 ameliorates Aβ pathogenesis-induced neuroinflammation in 5 × FAD mice

Life Sciences, Год журнала: 2024, Номер 357, С. 123085 - 123085

Опубликована: Окт. 1, 2024

Язык: Английский

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D30 alleviates β2-microglobulin -facilitated neurotoxic microglial responses in isoflurane/surgery-induced cognitive dysfunction in aged mice

Laboratory Investigation, Год журнала: 2024, Номер unknown, С. 102190 - 102190

Опубликована: Ноя. 1, 2024

Язык: Английский

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The compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer’s disease

Neural Regeneration Research, Год журнала: 2024, Номер 20(11), С. 3330 - 3344

Опубликована: Июль 10, 2024

JOURNAL/nrgr/04.03/01300535-202511000-00034/figure1/v/2024-12-20T164640Z/r/image-tiff Previous studies have shown that the compound ( E )-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one (D30), a pyromeconic acid derivative, possesses antioxidant and anti-inflammatory properties, inhibits amyloid-β aggregation, alleviates scopolamine-induced cognitive impairment, similar to phase III clinical drug resveratrol. In this study, we established mouse model of Alzheimer’s disease via intracerebroventricular injection fibrillar investigate effect D30 on amyloid-β–induced neuropathology. Our results showed alleviated promoted clearance from hippocampus cortex, suppressed oxidative stress, inhibited activation microglia astrocytes. also reversed loss dendritic spines synaptic protein expression. Notably, demonstrated exogenous introduced by greatly increased galectin-3 expression levels in brain, increase was blocked D30. Considering role clearing amyloid-β, inhibiting neuroinflammation, protecting synapses, improving cognition, study highlights potential as promising treatment target for patients with disease.

Язык: Английский

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Recent Advancements in the Treatment of Alzheimer’s Disease: A Multitarget-directed Ligand Approach

Current Medicinal Chemistry, Год журнала: 2023, Номер 31(37), С. 6032 - 6062

Опубликована: Дек. 27, 2023

: Alzheimer's disease (AD) is a neurodegenerative and one of the leading causes progressive dementia, affecting 50 million people worldwide. Many pathogenic processes, including amyloid β aggregation, tau hyperphosphorylation, oxidative stress, neuronal death, deterioration function cholinergic neurons, are associated with its progression. The one-compound-one-target treatment paradigm was unsuccessful in treating AD due to multifaceted nature disease. recent develop-ment multitarget-directed ligand research has been explored target complemen-tary pathways We aimed find key role progress MTDLs AD; thus, we searched for past ten years literature on “Pub-Med”, “ScienceDirect”, “ACS” “Bentham Science” using keywords neurodegen-erative diseases, Alzheimer’s disease, ligands. further filtered based quality work relevance AD. Thus, this review high-lights current advancement advantages ligands over tradi-tional single-targeted drugs their development treat

Язык: Английский

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