Computational screening and molecular dynamics of natural compounds targeting the SH2 domain of STAT3: a multitarget approach using network pharmacology

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract SH2 (Src Homology 2) domains play a crucial role in phosphotyrosine-mediated signaling and have emerged as promising drug targets, particularly cancer therapy. STAT3 (Signal Transducer Activator of Transcription 3), which contains an domain, plays pivotal progression immune evasion because it facilitates the dimerization STAT3, is essential for their activation subsequent nuclear translocation. domain-mediated inhibition disrupts this binding, reduces phosphorylation impairs dimerization. This study employed silico approach to screen potential natural compounds that could target domain inhibit its function. The phytomolecules (182455) were retrieved from ZINC 15 database docked using various modes like HTVS, SP, XP. exhibiting higher binding affinity selected. MM-GBSA was performed determine free energy, QikProp tool utilized assess pharmacokinetic properties hit compounds, narrowing down list candidates. Molecular dynamics simulations, thermal MM-GBSA, WaterMap analysis on exhibited favorable affinities characteristics. Based docking scores interactions, ZINC255200449, ZINC299817570, ZINC31167114, ZINC67910988 identified inhibitors. demonstrated superior stability molecular simulation analysis. Furthermore, DFT energetic electronic properties, HOMO LUMO sites predicted structure calculation. Additionally, network pharmacology map compounds’ interactions within biological networks, highlighting multitarget potential. Compound-target networks elucidate relationships between multiple along with associated pathways help minimize off-target effects. lead compound showed strong inhibitor, warranting further validation through vitro vivo studies. Graphical abstract

Язык: Английский

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Neuroprotective insights into epigallocatechin gallate (EGCG) for neurodegenerative disorders

Exploration of neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Neurodegenerative disorders, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are among the most significant health concerns worldwide, characterized by neuronal dysfunction, oxidative stress, neuroinflammation, protein misfolding. Epigallocatechin gallate, a green tea polyphenol, has been reported to possess multifaceted neuroprotective properties. It reduces stress through free radical scavenging, activation of antioxidant enzymes, stabilization mitochondrial function. also inhibits neuroinflammation modulation key signaling pathways. suppresses amyloid-beta aggregation in Alzheimer’s alpha-synuclein fibrillation thus attenuating toxic accumulation. Its activity induction autophagy promotion synaptic plasticity supports survival However, low bioavailability metabolic instability hinder its translation into clinic. Strategies nanoparticle encapsulation, structural modifications, combination therapies being explored overcome these challenges. Future research could establish epigallocatechin gallate as viable candidate for managing neurodegenerative disorders.

Язык: Английский

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Discovery of novel β-carboline/melatonin hybrids as STAT3 inhibitors for the treatment of lung cancer via increasing DNA damage

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер 127, С. 118227 - 118227

Опубликована: Май 6, 2025

Язык: Английский

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The Tumorigenic Effect of the High Expression of ABRACL in Glioma and Its Potential as a Therapeutic Target

Heliyon, Год журнала: 2024, Номер 10(17), С. e36597 - e36597

Опубликована: Авг. 28, 2024

Язык: Английский

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