Biomaterial Database

Design, synthesis, and biological evaluation of hydrazone incorporated 1,2,4-triazines as anticonvulsant agents. 2014

Mohammed Amir, and Israr Ali, and Mohd Zaheen Hassan, and Naveen Mulakayala

Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010433	Pentylenetetrazole	A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.	Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004597	Electroshock	Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states.	Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006835	Hydrazones	Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed)	Hydrazone
D000612	4-Aminobutyrate Transaminase	An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19.	Aminobutyrate Aminotransferase,GABA Transaminase,beta-Alanine Ketoglutarate Aminotransferase,GABA Aminotransferase,GABA-alpha-Ketoglutarate Aminotransferase,4 Aminobutyrate Transaminase,Aminotransferase, Aminobutyrate,Aminotransferase, GABA,Aminotransferase, GABA-alpha-Ketoglutarate,Aminotransferase, beta-Alanine Ketoglutarate,GABA alpha Ketoglutarate Aminotransferase,Ketoglutarate Aminotransferase, beta-Alanine,Transaminase, 4-Aminobutyrate,Transaminase, GABA,beta Alanine Ketoglutarate Aminotransferase