Autor según el artículo: Uribe, Laura A; Leonardo, Sandra; Nielsen, Thorbjorn Terndrup; Steinmann, Casper; Campas, Monica; Fragoso, Alex
Departamento: Enginyeria Química
Autor/es de la URV: CAMPAS HOMS, MONICA / Fragoso Sierra, Alex / Uribe Uribe, Laura Andrea
Código de proyecto: Grant agreement No. 713679
Palabras clave: Veratridine Neurotoxin Neuroblastoma 2-a Inclusion complex Cyclodextrin Cellbased assay Cell-based assay Beta-cyclodextrin toxicity solubilization sodium-channels neurotoxin neuroblastoma 2-a molecules inclusion complex glide derivatives cyclodextrin chemistry cell-based assay assay accurate docking
Resumen: Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the intoxication is mainly focused on treating the symptoms, meaning there is no specific antidote against VTD. In this pursuit, we were interested in studying the molecular interactions of VTD with cyclodextrins (CDs). CDs are supramolecular macrocycles with the ability to form host–guest inclusion complexes (ICs) inside their hydrophobic cavity. Since VTD is a lipid-soluble alkaloid, we hypothesized that it could form stable inclusion complexes with different types of CDs, resulting in changes to its physicochemical properties. In this investigation, we studied the interaction of VTD with ?-CD, ?-CD and sulfobutyl ether ?-CD (SBCD) by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. Docking and molecular dynamics studies confirmed the most stable configuration for the inclusion complexes. Finally, with an interest in understanding the effects of the VTD/CD molecular interactions, we performed cell-based assays (CBAs) on Neuro-2a cells. Our findings reveal that the use of different amounts of CDs has an antidote-like concentration-dependent effect on the cells, significantly increasing cell viability and thus opening opportunities for novel research on applications of CDs and VTD.
Áreas temáticas: Pharmacology & pharmacy Pharmaceutical science Medicina ii Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: monica.campas@urv.cat lauraandrea.uribe@estudiants.urv.cat lauraandrea.uribe@estudiants.urv.cat alex.fragoso@urv.cat
Identificador del autor: 0000-0002-1220-7100 0000-0003-4885-5393 0000-0003-4885-5393 0000-0003-4839-6094
Fecha de alta del registro: 2024-10-12
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Programa de financiación: Marie Skłodowska-Curie Actions - European Union's Horizon 2020 research and innovation programme
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Pharmaceutics. 14 (3): 598-
Referencia de l'ítem segons les normes APA: Uribe, Laura A; Leonardo, Sandra; Nielsen, Thorbjorn Terndrup; Steinmann, Casper; Campas, Monica; Fragoso, Alex (2022). Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability. Pharmaceutics, 14(3), 598-. DOI: 10.3390/pharmaceutics14030598
Acrónimo: MFP
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2022
Acción del progama de financiación: Martí i Franquès COFUND Doctoral Programme
Tipo de publicación: Journal Publications