In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reactants
2.2. Structure-Based Virtual Screening
2.3. In Vivo Assays
2.4. Patch Clamp Experiments
2.4.1. NaV1.2 and NaV1.1 Current Inhibition
2.4.2. CaV2.2 and CaV3.1 Current Inhibition
2.5. Statistics
3. Results
3.1. Virtual Screening
3.1.1. Validation
3.1.2. Molecular Docking
3.2. In Vivo Assays
3.3. Patch Clamp Experiments
3.3.1. NaV1.2 and NaV1.1 Current Inhibition
3.3.2. CaV2.2 and CaV3.1 Current Inhibition
3.4. Molecular Dynamics Simulations
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | Dose | Time | |
---|---|---|---|
0.5 h | 4 h | ||
5-Hexenoic acid | 30 mg/kg | 2/5 | 3/5 |
100 mg/kg | 0/5 | 3/5 | |
2-Aminooctanoic acid | 30 mg/kg | 4/5 | 4/5 |
100 mg/kg | 4/5 | 5/5 | |
9-Hydroxydecanoic acid | 30 mg/kg | 3/5 | 4/5 |
100 mg/kg | 4/5 | 3/5 | |
9-Phenylnonanoic acid | 30 mg/kg | 0/5 | 2/5 |
100 mg/kg | 2/5 | 4/5 |
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Barrionuevo, E.M.; Peralta, E.; Manzur De Nardi, A.; Monat, J.; Fallico, M.J.; Llanos, M.A.; Gavernet, L.; Mustafá, E.R.; Martin, P.; Talevi, A. In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation. Pharmaceutics 2024, 16, 996. https://doi.org/10.3390/pharmaceutics16080996
Barrionuevo EM, Peralta E, Manzur De Nardi A, Monat J, Fallico MJ, Llanos MA, Gavernet L, Mustafá ER, Martin P, Talevi A. In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation. Pharmaceutics. 2024; 16(8):996. https://doi.org/10.3390/pharmaceutics16080996
Chicago/Turabian StyleBarrionuevo, Emilia Mercedes, Estefanía Peralta, Agustín Manzur De Nardi, Juliana Monat, Maximiliano José Fallico, Manuel Augusto Llanos, Luciana Gavernet, Emilio Román Mustafá, Pedro Martin, and Alan Talevi. 2024. "In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation" Pharmaceutics 16, no. 8: 996. https://doi.org/10.3390/pharmaceutics16080996
APA StyleBarrionuevo, E. M., Peralta, E., Manzur De Nardi, A., Monat, J., Fallico, M. J., Llanos, M. A., Gavernet, L., Mustafá, E. R., Martin, P., & Talevi, A. (2024). In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation. Pharmaceutics, 16(8), 996. https://doi.org/10.3390/pharmaceutics16080996