Design, Synthesis and in-vivo Anticonvulsant activity of Some Novel Coumarin Derivatives

Abstract

Coumarin is an aromatic heterocyclic pharmacophore with six members that is found in a variety of synthetic and natural substances. When combined with the sulphonamide moiety, the special properties of the coumarin nucleus have expanded its range of biological action. N-[2-oxo-2-ethyl]-(2-oxo-2H-chromen-3-yl)-sulphonamide benzene, drug design, synthesis of novel compounds, molecular docking with the use of docking software (Schrödinger Maestro11.2 version), and spectrum characterisation. FTIR, high-resolution mass spectrometry, and NMR spectroscopy were among the spectroscopic methods utilized to confirm the structures of the compounds that were synthesized. Using a variety of techniques, studies were carried out to assess the pharmacokinetic properties of the drugs. Evaluation of anticonvulsant activity of the produced compounds (N-[2-oxo-2-(2-oxo-2H-chromen-3-yl)-ethyl]-benzenesulphonamide) have been done by employing the maximum electroshock seizures (MES) technique. This implies that the brain's GABA levels are elevated in some way as part of the anticonvulsive action mechanism. This evaluation was done by comparing the MES-induced HLTE duration with that of the control group. The produced compounds reduced HLTE at doses of 30 and 100 mg/kg, and no one died from MES-induced convulsions. The standard treatment, phenytoin (25 mg/kg i.p.), was chosen because it considerably reduced the duration of convulsions brought on by MES (***p<0.001) and prevented convulsions in several stages. The rotarod test device is used to assess the neurotoxicity of derivatives.