Multipotent Effect of Clozapine on Lipopolysaccharide-Induced Acetylcholinesterase, Cyclooxygenase-2,5-Lipoxygenase, and Caspase-3: In Vivo and Molecular Modeling Studies

Molecules, Год журнала: 2025, Номер 30(2), С. 266 - 266

Опубликована: Янв. 11, 2025

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits individuals at risk dementia, particularly those with neurodegenerative diseases, common cancers, diabetes type. Alzheimer’s disease (AD) the most cause acetylcholinesterase (AChE) key approach treating AD. Meanwhile, Caspase-3 catalyzes early events apoptosis, contributing to neurodegeneration subsequently Structure-based virtual screening US-FDA-approved molecules from ZINC15 database identified clozapine (CLOZ) as dual inhibitor COX-2 AChE, significant binding affinity. Further molecular docking CLOZ active site LOX also showed potential. Further, results were validated using dynamics simulation (MDS) studies, confirming docking. The MDS good interactions residues. was further assessed lipopolysaccharide (LPS)-challenged rats treated thirty days doses 5 10 mg/kg, p.o. demonstrated modulation COX-2, 5-LOX, Caspase-3, MDA LPS-induced brains. Additionally, expression level IL-10 measured. Our decrease levels MDA. decrement pro-inflammatory markers NF-κB, TNF-α, IL-6 an improvement TGF-β1. Overall, findings indicate that has neuroprotective against LPS-treated can be explored.

Язык: Английский

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Pregnenolone derivatives for the treatment of Alzheimer's disease: synthesis, and in vitro inhibition of amyloid β_1–42 peptide aggregation, acetylcholinesterase and carbonic anhydrase-II

RSC Advances, Год журнала: 2024, Номер 14(21), С. 14742 - 14757

Опубликована: Янв. 1, 2024

Pregnenolone-based derivatives have been synthesized to inhibit the protofibril formation in order reduce Aβ 1–42 production and prevent its aggregation.

Язык: Английский

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Promising thiazolidinedione-thiazole based multi-target and neuroprotective hybrids for Alzheimer’s disease: Design, synthesis, in-vitro, in-vivo and in-silico studies

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 287, С. 117327 - 117327

Опубликована: Фев. 3, 2025

Язык: Английский

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Synthesis, Pharmacological Evaluation, and Molecular Modeling of Phthalimide Derivatives as Monoamine Oxidase and Cholinesterase Dual Inhibitors

ACS Omega, Год журнала: 2025, Номер 10(10), С. 10385 - 10400

Опубликована: Март 4, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia and cognitive decline, associated with synaptic loss degeneration of cholinergic neurons. New multitarget inhibitors for monoamine oxidase (MAO) cholinesterase (ChE) enzymes are emerging as potential treatment strategy AD. Herein, we synthesized series N-benzyl-substituted biaryl phthalimide derivatives (3a-3m) encompassing potentially therapeutically active arenes/heteroarenes to serve compounds treating To improve their binding affinity well inhibitory activity against ChE MAO target proteins, comparable molecular structures were bearing electron-donating, electron-withdrawing, heterocyclic, fluorinated moieties comprehensive SAR. In vitro evaluation cholinesterases (AChE/BChE) oxidases (MAO-A/MAO-B) revealed that compound 3e had good potency AChE (IC50 = 0.24 μM) BChE 6.29 μM), while 3f the highest inhibition MAO-B 0.09 μM). Selected (3e,f) showed no cytotoxicity neuroblastoma cell line (SH-SY5Y) normal human embryonic HEK-293 cells. Moreover, they high blood-brain barrier penetration (PAMPA assay) reversible (ex vivo). docking studies, displayed ChEs MAO-B, respectively. silico ADMET studies MD simulation also carried out most potent (3e 3f), suggesting strong anti-Alzheimer agents.

Язык: Английский

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In vitro and In silico Anti-Alzheimer study of Rutin embedded with Zinc chloride loaded bovine serum albumin nanoparticles

Tissue and Cell, Год журнала: 2025, Номер 95, С. 102869 - 102869

Опубликована: Март 28, 2025

Язык: Английский

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Unveiling tyrosinase inhibition: exploring secondary metabolites from Fernandoa adenophylla through biological screening and molecular docking

Natural Product Research, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Апрель 21, 2025

The current study investigated the tyrosinase inhibitory activity of compounds extracted from Fernandoa adenophylla, complemented by in silico analysis. Using methanolic extract and chromatography, several were isolated tested for their effects against human mushroom enzymes. indanone derivative (Sample CC) emerged as most potent inhibitor, demonstrating 96.32% inhibition with an IC50 6.2 ± 0.9 µg/mL 91.3% 1.8 0.5 tyrosinase, surpassing standard Kojic acid. In docking studies further supported these findings, revealing strong binding interactions between Sample CC active site suggesting a robust mechanism. analysis interaction plots showed that interact key amino acid residues. These results highlight potential F. adenophylla natural inhibitors, offering promising alternatives therapeutic cosmetic applications.

Язык: Английский

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Pharmacological evaluation and binding behavior of 4,4′-diamino-2,2′-stilbene disulfonic acid with metal ions using spectroscopic techniques

Heliyon, Год журнала: 2024, Номер 10(14), С. e34639 - e34639

Опубликована: Июль 1, 2024

Industrial and human activities contribute significantly to the environmental contamination of heavy metal ions (HMIs), which have detrimental effects on aquatic life, plants, animals, causing major toxicological problems. The commercially available

Язык: Английский

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Ameliorative effects of gallic acid on tebuconazole–induced adverse effects in the cerebellum of adult albino rats: histopathological and immunohistochemical evidence

Ultrastructural Pathology, Год журнала: 2024, Номер 48(5), С. 351 - 366

Опубликована: Авг. 6, 2024

Tebuconazole (TEB) is a common triazole sterol demethylation inhibitor fungicide utilized to manage variety of diseases in crops like cereals, fruits, and vegetables. The aim this work was assess the effects TEB on structure cerebellum adult albino rats possible protective impact co-administration Gallic acid (GA). Four groups forty male were randomly selected, group I received corn oil through daily gavage for 4 weeks. Group II GA dissolved normal saline at dose 100 mg/kg weeks, III administered with its acceptable intake (0.02 body weight) IV both GA. For light microscopic, ultrastructural, immunohistochemical investigations, cerebellar specimens prepared. exposure led neuronal damage form degenerated Purkinje cells vacuolated cytoplasm, areas lost cells, basket appeared neuropil, granule clumped congested between them, dilated islands, weak positive bcl2 immunoreactions numerous GFAP-positive astrocytes. mitigated TEB-mediated histological changes cortex. We concluded that caused neurons rat cortex degenerate undergo apoptosis. had neuroprotective benefit against toxicity

Язык: Английский

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Gallic acid and loganic acid attenuate amyloid-β oligomer-induced microglia damage via NF-КB signaling pathway

Neuropharmacology, Год журнала: 2024, Номер 263, С. 110215 - 110215

Опубликована: Ноя. 12, 2024

Язык: Английский

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Antileishmanial potential of thiourea-based derivatives: design, synthesis and biological activity

RSC Advances, Год журнала: 2024, Номер 14(50), С. 37131 - 37141

Опубликована: Янв. 1, 2024

The evaluation of the results showed that compounds 4g and 20a–b could be promising leads/hits to enrich arsenal antileishmanial drug development.

Язык: Английский

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