Development of Donor–Acceptor Architecture-Based Potential Theranostic Fluorescent Probes for Alzheimer’s Disease

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

The cholinergic deficits and deposition of β-amyloid (Aβ) species are regarded as the key events contributing to progression Alzheimer's disease (AD). Herein, a series novel donor-acceptor architecture-type potential theranostic agents were designed, synthesized, evaluated for their against cholinesterase (ChE) enzymes detection Aβ species, which primary targets in development therapeutics AD. optimal compound/probe 18 containing benzothiazolium fluorophore with bifunctional electron-donating N-aryl piperazine scaffold exhibited potent inhibitory activities acetylcholinesterase (AChE; IC50 = 0.172 ± 0.011 μM) butyrylcholinesterase (BuChE; 1.376 0.141 μM). Measurement fluorescence properties showed that probe emission maxima (λem) >610 nm dimethyl sulfoxide (DMSO) >590 PBS, suitable imaging. In vitro studies demonstrated change characteristics high binding affinities (18; Kd 0.731 upon aggregates. affinity toward aggregates was further observed elavGAL4 > UAS Aβ, Drosophila larval brain sections, using imaging technique. vivo acute oral toxicity evaluation indicated safety profile lead 18. Moreover, behavioral including Y-maze object recognition tests signified administration compound improved cognitive spatial memory impairment at dose 10 20 mg/kg scopolamine-induced deficit model.

Язык: Английский

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Acetylcholinesterase Inhibitors from Carbamate and Benzo-fused Heterocyclic Scaffolds: Promising Therapeutics for Alzheimer’s Disease

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 18, 2025

Язык: Английский

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Exploring the pharmacological mechanism of Bu-Wang San on Alzheimer’s disease through multiple GEO datasets of the human hippocampus, network pharmacology, and metabolomics based on GC-MS and UPLC-Q/TOF-MS

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119994 - 119994

Опубликована: Май 1, 2025

Язык: Английский

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Design, synthesis, and evaluation of hydrazones as dual inhibitors of ryanodine receptors and acetylcholinesterases for Alzheimer’s disease

Bioorganic Chemistry, Год журнала: 2023, Номер 133, С. 106432 - 106432

Опубликована: Фев. 20, 2023

Язык: Английский

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1,2,3-Triazolo[4,5-b]aminoquinolines: Design, synthesis, structure, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, and molecular docking of novel modified tacrines

Bioorganic Chemistry, Год журнала: 2023, Номер 139, С. 106704 - 106704

Опубликована: Июль 6, 2023

Язык: Английский

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[3 + 2] Cycloaddition synthesis of new (nicotinonitrile-chromene) hybrids linked to pyrazole units as potential acetylcholinesterase inhibitors

Synthetic Communications, Год журнала: 2022, Номер 52(16), С. 1672 - 1684

Опубликована: Авг. 11, 2022

Two series of nicotinonitrile-linked chromenes attached to pyrazole units were synthesized in the current study. A [3 + 2] cycloaddition protocol was used produce target hybrids high yields by reacting respective nitrilimines, which generated situ action triethylamine on hydrazonoyl chlorides, with chromene-based enaminone. Generally, acetylcholinesterase and DPPH free radical inhibitory activity are related electronic properties para-substituent that is arene unit at pyrazole-C1. Furthermore, 3-acylpyrazole has a significant effect new hybrids' efficacy. At 25 50 µM concentrations, 3-acetylpyrazole p-OMe demonstrated best activity, inhibition percentages 75.8 88.3, respectively. previous hybrid most effective antioxidant an percentage 82.6 tested concentration µg/mL. According SwissADME, majority pyrazoles drug-like.

Язык: Английский

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[3+2] cycloaddition synthesis of new (nicotinonitrile‐chromene)‐based bis(pyrazole) hybrids as potential acetylcholinesterase inhibitors

Journal of Heterocyclic Chemistry, Год журнала: 2022, Номер 60(1), С. 156 - 160

Опубликована: Окт. 23, 2022

Abstract A [3+2] cycloaddition protocol was used to prepare two series of (nicotinonitrile‐chromene)‐based bis(pyrazoles) in 82%–91% yields. The involved the reaction nitrilimines, which were generated situ by action triethylamine on hydrazonoyl chlorides, with respective bis(enaminone). At concentrations tested, bis(pyrazole) linked 1‐(4‐methoxyphenyl) and 3‐acetyl units had best acetylcholinesterase DPPH‐free radical inhibitory activity.

Язык: Английский

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Ultrasound‐Mediated Synthesis of New (Piperazine‐Chromene)‐Linked Bis(thieno[2,3‐b]pyridine) Hybrids as Potential Anti‐acetylcholinesterase

ChemistrySelect, Год журнала: 2022, Номер 7(41)

Опубликована: Ноя. 2, 2022

Abstract Using ultrasound irradiation and the eco‐friendly piperazine, two series of (piperazine‐chromene)‐linked bis(thieno[2,3‐b]pyridine) hybrids attached to various arene or chromene units were efficiently prepared. Therefore, target prepared by reacting bis(pyridine‐2(1 H )‐thione) with equivalents appropriate α‐haloketones in presence 1.4 piperazine. The reaction mixture was subjected ultrasonic irradiations at 60 °C for 20–40 min produce desired products 87–96 % yields. At concentrations 15 25 μM, new tested anti‐acetylcholinesterase activity, as well their ability quench DPPH free radicals a concentration μg/mL. Generally, unit thienopyridine‐C2 has significant effect on inhibitory activity hybrids. Moreover, electronic properties substituent chromene‐C6 influence activity. bis(thienopyridine) hybrid 6‐methoxy‐2 ‐chromen‐2‐one demonstrated best previous concentrations, inhibition percentages 69.1 85.4. Additionally, an percentage 84.4, most effective anti‐DPPH

Язык: Английский

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Access to 8-Aminoindolizine Fused with Quinone via Cu(OAc)2-Catalyzed Domino [4+2] Annulation

Synthesis, Год журнала: 2024, Номер 56(11), С. 1799 - 1806

Опубликована: Фев. 1, 2024

Abstract Cu(OAc)2-catalyzed [4+2] annulation of N-substituted pyrrole-2-carbonitriles with quinones allowed access to a wide range 8-aminoindolizines fused through domino process involving sequence intermolecular Michael addition, Thorpe–Ziegler type cyclization, and aromatization. Biological evaluation the resulting quinone-8-aminoindolizine hybrids revealed significant anticancer effects these compounds in human hepatocellular cells (HepG2) prostate adenocarcinoma (PC-3).

Язык: Английский

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Synthesis and Neurobehavioral Evaluation of a Potent Multitargeted Inhibitor for the Treatment of Alzheimer’s Disease

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Июль 15, 2024

Язык: Английский

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