title: Preliminary anticonvulsant and toxicity screening of substituted benzylidenehydrazinyl-N-(6-substituted benzo[d]thiazol-2-yl)propanamides.
abstract: Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)-propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). Synthesized compounds were characterized by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo anticonvulsant screening (phase I) was performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Based on anticonvulsant screening results, two compounds, 5h and 5p, were found to be most active; they exhibited activity comparable to standard drugs phenytoin (PHY) and carbamazepine (CBZ). These active compounds were subjected to phase II and phase III screening, where they displayed much higher protective index (PI) in comparison to the standard drugs. In phase IV screening, the bioavailability of active compounds was assessed on oral administration. Further, preliminary safety profiles of 5h and 5p were evaluated by the neurotoxicity testing and liver enzyme estimation.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 1100062, India.
authors.forename: Ruhi
authors.initials: R
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 1100062, India.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy* / Q000473:pathology; D006860:Hydrogen Bonding; D010672:Phenytoin / Q000737:chemistry; D012640:Seizures / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D052160:Benzothiazoles; D010672:Phenytoin; C005465:benzothiazole