title: Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides.
abstract: Thirty six new N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothioamides were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was 2-[4-(4-chlorophenoxy)benzylidene]-N-(4-fluorophenyl)hydrazinecarbothioamide PC 31 which showed 100% protection at 0.5 h in the 6 Hz test. Compound 2-[4-(4-bromophenoxy) benzylidene]-N-(4-bromophenyl) hydrazinecarbothioamide PC 23 was found to be active in both the MES and 6 Hz test. A computational study was carried out from calculation of a pharmacophore pattern and the prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in the Lamarckian genetic algorithm based on flexible docking studies.
authors.affiliation: Department of Pharmaceutical Chemistry, S.D. College of Pharmacy and Vocational Studies, Muzaffarnagar 251001, India. tripathilaxmi@rediffmail.com
authors.forename: Laxmi
authors.initials: L
authors.lastname: Tripathi
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Ranjit
authors.initials: R
authors.lastname: Singh
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D004827:Epilepsy / Q000188:drug therapy; D006860:Hydrogen Bonding; D008297:Male; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism; D013854:Thioamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A; D013854:Thioamides