1. Design, synthesis, and biological evaluation of hydrazone incorporated 1,2,4-triazines as anticonvulsant agents.
- Author
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Amir M, Ali I, Hassan MZ, and Mulakayala N
- Subjects
- 4-Aminobutyrate Transaminase chemistry, 4-Aminobutyrate Transaminase metabolism, Animals, Anticonvulsants metabolism, Binding Sites, Catalytic Domain, Computer-Aided Design, Disease Models, Animal, Electroshock, Female, Humans, Hydrazones metabolism, Male, Mice, Molecular Docking Simulation, Molecular Structure, Pentylenetetrazole, Protein Binding, Protein Conformation, Seizures etiology, Seizures physiopathology, Structure-Activity Relationship, Triazines metabolism, Anticonvulsants chemical synthesis, Anticonvulsants pharmacology, Drug Design, Hydrazones chemical synthesis, Hydrazones pharmacology, Seizures prevention & control, Triazines chemical synthesis, Triazines pharmacology
- Abstract
New hydrazone incorporated triazines were designed and synthesized using an appropriate synthetic route with regard to essential pharmacophores, and evaluated for their anticonvulsant activity through maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole-induced seizure (scPTZ) screenings. Among the tested compounds, 4-[{2-(5-(3-chlorobenzyl)-3-phenyl-1,2,4-triazine-6-yl)hydrazono}methyl]-N,N-dimethylaniline 6k (MES ED50 54.31, scPTZ ED50 92.01) and 4-[{2-(5-(4-chlorobenzyl)-3-phenyl-1,2,4-triazine-6-yl)hydrazono}methyl]-N,N-dimethylaniline 6r (MES ED50 46.05, scPTZ ED50 83.90) emerged as the most active anticonvulsant agents having GABAergic effects. Compounds 6k and 6r also showed lesser CNS depressant effect than the standard drug carbamazepine. To obtain further insights into the binding interactions of these molecules, molecular docking studies were carried out., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
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