Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent
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 t...
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| Format: | Article |
| Language: | English |
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Sciendo
2016-09-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.1515/acph-2016-0023 |
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| author | Shakya Ashok K. Kamal Mehnaz Balaramnavar Vishal M. Bardaweel Sanna K. Naik Rajashri R. Saxena Anil K. Siddiqui H. H. |
| author_facet | Shakya Ashok K. Kamal Mehnaz Balaramnavar Vishal M. Bardaweel Sanna K. Naik Rajashri R. Saxena Anil K. Siddiqui H. H. |
| author_sort | Shakya Ashok K. |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1846-9558 |
| language | English |
| last_indexed | 2024-12-22T06:42:21Z |
| publishDate | 2016-09-01 |
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| spelling | doaj.art-1ef2da009c9c4175ade14e09656838c42022-12-21T18:35:24ZengSciendoActa Pharmaceutica1846-95582016-09-0166335337210.1515/acph-2016-0023acph-2016-0023Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agentShakya Ashok K.0Kamal Mehnaz1Balaramnavar Vishal M.2Bardaweel Sanna K.3Naik Rajashri R.4Saxena Anil K.5Siddiqui H. H.6Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University Amman, 19328, JordanFaculty of Pharmacy, Integral University Kursi Road, Lucknow 226026 (U. P.), IndiaMedicinal and Process Chemistry Division, Central Drug Research Institute Lucknow-226001 (U. P.), IndiaFaculty of Pharmacy The University of Jordan, Amman, JordanFaculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University Amman, 19328, JordanMedicinal and Process Chemistry Division, Central Drug Research Institute Lucknow-226001 (U. P.), IndiaFaculty of Pharmacy, Integral University Kursi Road, Lucknow 226026 (U. P.), IndiaA 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.https://doi.org/10.1515/acph-2016-0023benzofurananticonvulsantneurotoxicitygaba-atpharmacophore modelingdockingmolegro virtual docker 4.0 |
| spellingShingle | Shakya Ashok K. Kamal Mehnaz Balaramnavar Vishal M. Bardaweel Sanna K. Naik Rajashri R. Saxena Anil K. Siddiqui H. H. Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent Acta Pharmaceutica benzofuran anticonvulsant neurotoxicity gaba-at pharmacophore modeling docking molegro virtual docker 4.0 |
| title | Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent |
| title_full | Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent |
| title_fullStr | Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent |
| title_full_unstemmed | Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent |
| title_short | Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent |
| title_sort | design synthesis and evaluation of benzofuran acetamide scaffold as potential anticonvulsant agent |
| topic | benzofuran anticonvulsant neurotoxicity gaba-at pharmacophore modeling docking molegro virtual docker 4.0 |
| url | https://doi.org/10.1515/acph-2016-0023 |
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