Synergistic Biomedical Potential and Molecular Docking Analyses of Coumarin–Triazole Hybrids as Tyrosinase Inhibitors: Design, Synthesis, In Vitro Profiling, and In Silico Studies

Pharmaceuticals, Год журнала: 2024, Номер 17(4), С. 532 - 532

Опубликована: Апрель 20, 2024

The tyrosinase enzyme has a vital role in the browning of vegetables and fruits biosynthesis melanin. In this work, we synthesized diverse library coumarin–triazole hybrids, these compounds were characterized by using suitable analytical techniques. Our research work extends beyond synthetic effort to explore therapeutic potential compounds. We put through meticulous vitro screening against enzyme, coumarin derivatives evinced good IC50 values range 0.339 ± 0.25 µM 14.06 0.92 µM. compounds, six found be more potent than standard ascorbic acid (IC50 = 11.5 1.00), among them, 17e 17f, being most active, exhibited remarkable anti-tyrosinase potential, with μM 3.148 0.23 μM, respectively. Furthermore, an silico modeling study was carried out determine key interactions protein (PDB ID: 2Y9X) thus authenticate our experimental findings. quantitative SAR studies correlation between their activity. docking verified results, ligand showed interaction core residues tyrosinase. This not only expands field hybrid synthesis but also provides valuable insights for development novel inhibitors.

Язык: Английский

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Looking beneath the surface: Melanin-like nanoscaled polydopamine coating for “green” hair dyeing

Progress in Organic Coatings, Год журнала: 2025, Номер 201, С. 109112 - 109112

Опубликована: Фев. 5, 2025

Язык: Английский

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Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 152, С. 105287 - 105287

Опубликована: Июнь 15, 2023

Язык: Английский

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Oxidation of dopamine and related catechols in dopaminergic brain regions in Parkinson’s disease and during ageing in non-Parkinsonian subjects

Journal of Neural Transmission, Год журнала: 2024, Номер 131(3), С. 213 - 228

Опубликована: Янв. 18, 2024

Язык: Английский

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Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe

Analytical Chemistry, Год журнала: 2024, Номер 96(18), С. 7082 - 7090

Опубликована: Апрель 23, 2024

Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, levels of which can serve as an indicator assessing severity progression PD. This renders specific detection visualization TH strategically vital way to meet above demands. However, fluorescent probe still missing. Herein, three rationally designed wash-free ratiometric probes were proposed. Among them,

Язык: Английский

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Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-related Oxidative Stress and Other Bioenergetic Challenges

Опубликована: Янв. 3, 2024

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons substantia nigra pars compacta (SNc). Why SNc DA are especially vulnerable and why idiopathic PD has only been found humans still puzzling. two main underlying factors neuron vulnerability appear related to high production, namely (i) toxic effects cytoplasmic metabolism (ii) continuous cytosolic Ca2+ oscillations absence Ca2+-buffer protein calbindin. Both cause oxidative stress by producing highly reactive quinones increasing intra-mitochondrial concentrations, respectively. High expression human cell bodies suggested abundant presence DA-derived pigment neuromelanin, which not such abundance other species associated with toxicity at higher levels. created their production system, despite that SN does use unusually amounts energy, explains sensitive various genetic environmental create mitochondrial damage thereby promote PD. Aging increases multiple risk for PD, and, a large extent, accelerated aging. To prevent neurodegeneration, possible approaches discussed here (1) reducing accumulation, (2) blocking oscillations, (3) providing bioenergetic support.

Язык: Английский

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Catecholamines and Parkinson’s disease: tyrosine hydroxylase (TH) over tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH1) to cytokines, neuromelanin, and gene therapy: a historical overview

Journal of Neural Transmission, Год журнала: 2023, Номер 131(6), С. 617 - 630

Опубликована: Авг. 28, 2023

Язык: Английский

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A new strategy for the treatment of Parkinson’s disease: Discovery and bio-evaluation of the first central-targeting tyrosinase inhibitor

Bioorganic Chemistry, Год журнала: 2024, Номер 150, С. 107612 - 107612

Опубликована: Июль 2, 2024

Язык: Английский

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Modulating efficient differentiation of neural stem cells into neurons by using plasmonic nanoparticles and the NIR II irradiation to boost therapy of Parkinson’s disease

Nano Today, Год журнала: 2024, Номер 57, С. 102392 - 102392

Опубликована: Июль 6, 2024

Язык: Английский

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Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 25, 2024

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized nerve degeneration distal to the site injury resulting in long periods skeletal muscle denervation. During this period, fibers atrophy frequently become incapable "accepting" innervation because slow speed axon regeneration post injury. We hypothesize that reprogramming an embryonic-like state may preserve its reinnervation capability following PNI. To end, we generate a mouse model which NANOG, pluripotency-associated transcription factor expressed locally upon delivery doxycycline (Dox) polymeric vehicle. NANOG expression upregulates percentage Pax7+ nuclei eMYHC along with other genes are involved development. In sciatic transection model, leads upregulation key associated myogenesis, neurogenesis neuromuscular junction (NMJ) formation. Further, mice demonstrate extensive overlap between synaptic vesicles NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, show greater improvement motor function as compared wild-type (WT) animals, evidenced improved toe-spread reflex, EMG responses isometric force production. conclusion, can be effective strategy improve functional outcomes after

Язык: Английский

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