1. Synthesis and biological evaluation of new antiseizure compounds derived from valproic acid.
- Author
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Garofalo FM, Sbaraglini ML, Barrionuevo EM, Peralta E, Bonifazi EL, Talevi A, and Gavernet L
- Subjects
- Mice, Animals, Anticonvulsants pharmacology, Anticonvulsants therapeutic use, Seizures chemically induced, Seizures drug therapy, Pentylenetetrazole therapeutic use, Disease Models, Animal, Dose-Response Relationship, Drug, Valproic Acid pharmacology, Valproic Acid therapeutic use, Epilepsy drug therapy
- Abstract
Background: New hybrid compounds were synthesized by linking the valproic acid (VPA) structure with other anticonvulsant/anti-inflammatory scaffolds. Materials & methods: The chemistry involved the incorporation of the linker oxymethyl ester into VPA, followed by reaction with the second scaffold. The antiseizure effects were investigated by the maximal electroshock seizure test, and the most active compound was additionally evaluated in the 6 Hz test and pentylenetetrazol test in mice. Results: The compounds showed protection against seizures. The hybrid structure with the butylparaben scaffold exhibited an ED
50 of 8.265 mg/kg (0.0236 mmol/Kg) in the maximal electroshock seizure test and 50.00 mg/kg (0.147 mmol/kg) in the 6 Hz test. Conclusion: The antiseizure activity of the synthesized compounds highlighted the potential of hybrid structures to treat multifactorial diseases such as epilepsy.- Published
- 2023
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