2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures: synthesis and pharmacological evaluation.
Various 2,4-dimethoxyphenylsemicarbazones were synthesized starting from 2,4-dimethoxyaniline via a phenylcarbamate intermediate. The structures were confirmed by spectral and elemental analyses. The anticonvulsant activity of the synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure, subcutaneous pentylenetetrazole, and subcutaneous strychnine-induced seizure screens. Nine compounds exhibited protection in all the three seizure models, and N1-(2,4-dimethoxyphenyl)-N4-(propan-2-one)semicarbazone (17) emerged as the most active compound with no neurotoxicity. These compounds were found to elevate gamma-aminobutyric acid (GABA) levels in the midbrain and medulla oblongata regions equipotent to clobazam.
Thirumurugan
Rathinasabapathy
R
Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India.
Sriram
Dharmarajan
D
Saxena
Amrita
A
Stables
James
J
Yogeeswari
Perumal
P
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D012640:Seizures / Q000378:metabolism / Q000517:prevention & control*; D012664:Semicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D012664:Semicarbazones; D005680:gamma-Aminobutyric Acid; D010100:Oxygen