Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a
Nine previously undescribed brefeldin A (BFA) derivatives (1–9), together with one known compound 4-epi-brefeldin A (10), were isolated from an endophytic fungus Penicillium brefeldianum F4a. The chemical structures were elucidated using NMR and HRESIMS. ECD analysis and Mosher's method were us...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S187853522300850X |
| _version_ | 1797390560283066368 |
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| author | Yan Bai Duo Ren Xinlei Xue Weixian Gao Jiangchun Hu Huaqi Pan |
| author_facet | Yan Bai Duo Ren Xinlei Xue Weixian Gao Jiangchun Hu Huaqi Pan |
| author_sort | Yan Bai |
| collection | DOAJ |
| description | Nine previously undescribed brefeldin A (BFA) derivatives (1–9), together with one known compound 4-epi-brefeldin A (10), were isolated from an endophytic fungus Penicillium brefeldianum F4a. The chemical structures were elucidated using NMR and HRESIMS. ECD analysis and Mosher's method were used to confirm the absolute configurations of 1–9. The inhibitory activity of all isolated BFA derivatives (1–10) on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was evaluated in vitro. The bioassay results suggested that neobrefeldin (1) and brefeldin H (2) exhibited higher potent and selective AChE inhibitory activity (IC50 = 0.12 and 0.28 μM) than the therapeutic drug galantamine for Alzheimer's disease (AD) (IC50 = 0.66 µM), whereas only neobrefeldin (1) displayed weak inhibitory activity against BuChE (IC50 = 175.04 µM). Moreover, a molecular docking analyses was performed and showed compounds 1 and 2 were dual binding site AChE inhibitors. It is worth noting that neobrefeldin (1) showed a better binding affinity with the peripheral anionic site through the hydrogen bonding interaction with Tyr124 than brefeldin H (2), resulting in better AChE inhibitory activity. These findings not only provide a promising AChE inhibitor neobrefeldin (1) for developing agents against early AD, but also provide a valuable perspective for better understanding its AChE inhibition activity. |
| first_indexed | 2024-03-08T23:12:40Z |
| format | Article |
| id | doaj.art-950d64cbf82446aea1d53c543cf6d1a0 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-08T23:12:40Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-950d64cbf82446aea1d53c543cf6d1a02023-12-15T07:23:23ZengElsevierArabian Journal of Chemistry1878-53522024-01-01171105388Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4aYan Bai0Duo Ren1Xinlei Xue2Weixian Gao3Jiangchun Hu4Huaqi Pan5Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China; School of Pharmacy, China Medical University, Shenyang 110016, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, ChinaInstitute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China; Corresponding author.Nine previously undescribed brefeldin A (BFA) derivatives (1–9), together with one known compound 4-epi-brefeldin A (10), were isolated from an endophytic fungus Penicillium brefeldianum F4a. The chemical structures were elucidated using NMR and HRESIMS. ECD analysis and Mosher's method were used to confirm the absolute configurations of 1–9. The inhibitory activity of all isolated BFA derivatives (1–10) on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was evaluated in vitro. The bioassay results suggested that neobrefeldin (1) and brefeldin H (2) exhibited higher potent and selective AChE inhibitory activity (IC50 = 0.12 and 0.28 μM) than the therapeutic drug galantamine for Alzheimer's disease (AD) (IC50 = 0.66 µM), whereas only neobrefeldin (1) displayed weak inhibitory activity against BuChE (IC50 = 175.04 µM). Moreover, a molecular docking analyses was performed and showed compounds 1 and 2 were dual binding site AChE inhibitors. It is worth noting that neobrefeldin (1) showed a better binding affinity with the peripheral anionic site through the hydrogen bonding interaction with Tyr124 than brefeldin H (2), resulting in better AChE inhibitory activity. These findings not only provide a promising AChE inhibitor neobrefeldin (1) for developing agents against early AD, but also provide a valuable perspective for better understanding its AChE inhibition activity.http://www.sciencedirect.com/science/article/pii/S187853522300850XCholinesterase inhibitorsEndophytic fungiPenicillium brefeldianumBrefeldin A derivativesMolecular docking |
| spellingShingle | Yan Bai Duo Ren Xinlei Xue Weixian Gao Jiangchun Hu Huaqi Pan Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a Arabian Journal of Chemistry Cholinesterase inhibitors Endophytic fungi Penicillium brefeldianum Brefeldin A derivatives Molecular docking |
| title | Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a |
| title_full | Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a |
| title_fullStr | Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a |
| title_full_unstemmed | Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a |
| title_short | Structurally diverse brefeldin A derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus Penicillium brefeldianum F4a |
| title_sort | structurally diverse brefeldin a derivatives as potent and selective acetylcholinesterase inhibitors from an endophytic fungus penicillium brefeldianum f4a |
| topic | Cholinesterase inhibitors Endophytic fungi Penicillium brefeldianum Brefeldin A derivatives Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S187853522300850X |
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