Anticonvulsant and neurotoxicity evaluation of some N(4) phenyl substituted pyridyl semicarbazones.
A series of 4-aryl substituted semicarbazones of pyridyl carbaldehyde and pyridyl methyl ketone were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. The structure of synthesized compounds were confirmed by IR spectroscopy, PMR spectroscopy and nitrogen estimation. All the compounds were evaluated for anticonvulsant activity and neurotoxicity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Majority of compounds exhibited significant anticonvulsant activity after intraperitoneal administration. The results obtained showed that 85.7 % of the compounds afforded protection in the MES test and 64.2 % of the total compounds afforded protection in ScPTZ test. Some of them also showed good activity after oral administration. In this study (Methyl-4- pyridyl) ketone -N(4)- (p- chloro phenyl) substituted semicarbazone emerged as most active derivative showing activity at 100 mg/kg in both the test with prolonged duration of action. In the present study semicarbazones of pyridyl containing carbonyl compounds emerges as the lead molecule, showing broad spectrum of activity with low neurotoxicity and prolong duration of action on oral administration. Thus these may be utilized for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity.
Aggarwal
Navneet
N
Lachoo Memorial College of Science and Technology, Pharmacy Wing, Jodhpur, Rajasthan, India. contactnavneet@yahoo.com
Mishra
Pradeep
P
Nagori
Badri Prakash
BP
Aggarwal
Ruchi
R
Jain
Jainendra
J
D000818:Animals; D000927:Anticonvulsants; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes; D010433:Pentylenetetrazole / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy*; D012664:Semicarbazones; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D012664:Semicarbazones; D010433:Pentylenetetrazole