Author, as appears in the article.: Uribe, Laura A; Leonardo, Sandra; Nielsen, Thorbjorn Terndrup; Steinmann, Casper; Campas, Monica; Fragoso, Alex
Department: Enginyeria Química
URV's Author/s: CAMPAS HOMS, MONICA / Fragoso Sierra, Alex / Uribe Uribe, Laura Andrea
Project code: Grant agreement No. 713679
Keywords: 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
Abstract: 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.
Thematic Areas: Pharmacology & pharmacy Pharmaceutical science Medicina ii Farmacia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: monica.campas@urv.cat lauraandrea.uribe@estudiants.urv.cat lauraandrea.uribe@estudiants.urv.cat alex.fragoso@urv.cat
Author identifier: 0000-0002-1220-7100 0000-0003-4885-5393 0000-0003-4885-5393 0000-0003-4839-6094
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/1999-4923/14/3/598
Funding program: Marie Skłodowska-Curie Actions - European Union's Horizon 2020 research and innovation programme
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Pharmaceutics. 14 (3): 598-
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
Acronym: MFP
Article's DOI: 10.3390/pharmaceutics14030598
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Funding program action: Martí i Franquès COFUND Doctoral Programme
Publication Type: Journal Publications