Synthesis and evaluation of some novel essential amino acid-benzofuran-acetamide/propanamide/butanamide hybrids as potential anticonvulsant agents

In this study, some new essential amino acid-benzofuran-acetamide/propanamide/butanamide hybrid derivatives were synthesized. The structures of the synthesized compounds were confirmed on the basis of their elemental and spectral analyses. Their anti-seizure activity was investigated using maximal electroshock seizure (MES) and subcutaneous metrazol (scMET) seizure tests in mice. Neurotoxicity (NT) of the synthesized compounds was also determined by the rotarod test. Derivatives exhibited favorable protection in both MES and scMET tests with high safety levels in NT test. The derivatives have proven significant activity in mice and could be suggested as potential anticonvulsant lead compounds. All leucine-chlorobenzoyl benzofuran-acetamide/propanamide/ butanamide hybrid derivatives (6b, 7b, and 8b) showed significant anticonvulsant activity in MES model. Compound 8b also demonstrated potent anticonvulsant activity against scMET test. The compound 8b showed maximum activity and would be considered as a lead for further optimization as anticonvulsant agent.