Acta Pharm. 62 (2012) 263-286

full paper

Review

Semicarbazone – versatile therapeutic pharmacophore for fragment based anticonvulsant drug design

SURENDRA NATH PANDEYA

snpande65@yahoo.co.in

Department of Pharmacy, Saroj Institute of Technology and Management Ahimamau, Sultanpur Road Lucknow-226002 (U.P.), India

Accepted July 17, 2012

During the last fifteen years semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) has been discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroskock (MES) ED₅₀ (i.p. 12.9 mg kg^-1). In MES (oral screen), this compound has protective index (PI = TD₅₀/ED₅₀ >315) higher than carbamazepine (PI 101), phenytoin (PI >21.6) and valproate (PI 2.17). This compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole (ScPTZ), subcutaneous strychnine (ScSTY), subcutaneous picrotoxine (ScPIC) and subcutaneous bicculline (ScBIC). Semicarbazones are also GABA-transaminase inhibitors. Extensive structure-activity relationship has demonstrated that F, Cl, Br and NO₂ substitutents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.

Keywords: semicarbazone, anticonvulsant, Na⁺ channel blocker