title: Design, synthesis, and biological evaluation of hydrazone incorporated 1,2,4-triazines as anticonvulsant agents.
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.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Amir
authors.forename: Israr
authors.initials: I
authors.lastname: Ali
authors.forename: Mohd Zaheen
authors.initials: MZ
authors.lastname: Hassan
authors.forename: Naveen
authors.initials: N
authors.lastname: Mulakayala
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D017076:Computer-Aided Design; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010433:Pentylenetetrazole; D011485:Protein Binding; D011487:Protein Conformation; D012640:Seizures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D006835:Hydrazones; D014227:Triazines; C093444:1,2,4-triazine; D000612:4-Aminobutyrate Transaminase; D010433:Pentylenetetrazole
keywords: Anticonvulsant; CNS depression; GABA; Hydrazone; Triazine