Synthesis of some novel N4-(naphtha[1,2-d]thiazol-2-yl)semicarbazides as potential anticonvulsants.
A series of N(4)-(naphtha[1,2-d]thiazol-2-yl)semicarbazides were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure tests and minimal motor impairment was determined by rotorod test. A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. Some of the selected compounds were evaluated orally in rats for activity in scPTZ test at several time points (50 mg/kg). The most active compounds carry bromo, fluoro and nitro substituents at 4-position in the phenyl ring. The biochemical estimations of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) from brain homogenate not only clearly implicated the role of free radicals in PTZ-induced convulsion but also explained the possible mechanism of protective effect of semicarbazides, through the reduced formation of MDA and increased formation of SOD and GSH-Px.
Azam
Faizul
F
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana 136119, India. azamfaizul@yahoo.co.in
Alkskas
Ismail A
IA
Khokra
Sukhbir Lal
SL
Prakash
Om
O
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001923:Brain Chemistry; D005979:Glutathione Peroxidase / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D012640:Seizures / Q000188:drug therapy; D012663:Semicarbazides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000032:analysis
D000927:Anticonvulsants; D012663:Semicarbazides; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase