Synthesis and anticonvulsant and neurotoxicity evaluation of N4-phthalimido phenyl (thio) semicarbazides.
The phenyl (thio) semicarbazide derivatives of phthalimido pharmacophore were synthesized and evaluated for their anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was performed using intraperitoneal (i.p.), maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ) and subcutaneous strychnine (sc STY)-induced seizure threshold tests in mice. Compound 2c afforded protection in all the three screens. Compounds except 1d, 2a and 2d showed no neurotoxicity up to 300 mg/kg. Compounds 1a, 1b, 2c, 2d, 2g and 2i were found to show oral MES activity. The compounds exhibited CNS depression and behavioral despair side effects, lesser than the conventional antiepileptic drugs.
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani 333031, India. pyogie_2000@rediffmail.com
P
P
Yogeeswari
D
D
Sriram
V
V
Saraswat
J Vaigunda
JV
Ragavendran
M Mohan
MM
Kumar
S
S
Murugesan
R
R
Thirumurugan
J P
JP
Stables
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000633:toxicity*
D000927:Anticonvulsants; D012663:Semicarbazides