Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agentReport as inadecuate




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Acta Pharmaceutica, Vol.66 No.3 September 2016. -

A series of N-2-benzoyl-4-chlorobenzoyl-benzofuran-3-yl-2-substituted acetamide derivatives 4a-l, 5a-l was synthesized in good yield. All the synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures MES model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg–1 body mass during 0.5–4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, compounds 5i N-2-4-chlorobenzoyl-benzofuran-3-yl-2-cyclohexylmethylamino-acetamide and 5c N-2-4-chlorobenzoyl-benzofuran-3-yl-2-4-methylpiperidin-1-ylacetamide demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas compound 5f N-2-4-chlorobenzoyl-benzofuran-3-yl-2-4-furan-2-carbonyl-piperazin-1-yl acetamide exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg–1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg–1 ~23.4 to 127.6 mg kg–1 body mass. The pharmacophore mapping of the examined compounds on standard drugs phenobarbital, phenytoin, ralitolin and carbamazepine strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

benzofuran; anticonvulsant; neurotoxicity; GABA-AT; pharmacophore modeling; docking; Molegro Virtual Docker 4.0



Author: ASHOK K. SHAKYA - orcid.org-0000-0002-2387-6940 ; Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University, Amman, 1

Source: http://hrcak.srce.hr/



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