<abstract xmlns="http://www.w3.org/1999/xhtml"> 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 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, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) 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.</abstract>

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 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, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) 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.

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

Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University Amman, 19328, Jordan

Faculty of Pharmacy, Integral University Kursi Road, Lucknow 226026 (U. P.), India

Department of Pharmaceutical Chemistry, College of Pharmacy (Female Section), Prince Sattam Bin Abdulaziz University, Al-Kharj 11942 Kingdom of Saudi Arabia

Medicinal and Process Chemistry Division, Central Drug Research Institute Lucknow-226001 (U. P.), India

Department of Pharmaceutical Chemistry Global Institute of Pharmaceutical Education and Research, Kashipur 244713 Uttarakhand, India

Faculty of Pharmacy The University of Jordan, Amman, Jordan

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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 synthesized...

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

Publié en ligne: 29 juin 2016

Pages: 353 - 372

Accepté: 11 janv. 2016

DOI: https://doi.org/10.1515/acph-2016-0023

Mots clés
benzofuran, anticonvulsant, neurotoxicity, GABA-AT, pharmacophore modeling, docking, Molegro Virtual Docker 4.0

© by Ashok K. Shakya

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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

Publié en ligne: 29 juin 2016

Pages: 353 - 372

Accepté: 11 janv. 2016

DOI: https://doi.org/10.1515/acph-2016-0023

Mots clésbenzofuran, anticonvulsant, neurotoxicity, GABA-AT, pharmacophore modeling, docking, Molegro Virtual Docker 4.0

© by Ashok K. Shakya

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
benzofuran, anticonvulsant, neurotoxicity, GABA-AT, pharmacophore modeling, docking, Molegro Virtual Docker 4.0