Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity
Selective blockade of the serotonin 5-HT2A receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT2A receptor using AutoDock. Selected compounds with h...
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2013
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| Online Access: | http://eprints.um.edu.my/8149/ http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12069/abstract |
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| author | Munusamy, V. Yap, B.K. Buckle, M.J.C. Doughty, S.W. Chung, L.Y. |
| author_facet | Munusamy, V. Yap, B.K. Buckle, M.J.C. Doughty, S.W. Chung, L.Y. |
| author_sort | Munusamy, V. |
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| content_provider | Universiti Malaya |
| content_source | UM Research Repository |
| continent | Asia |
| country | Malaysia |
| description | Selective blockade of the serotonin 5-HT2A receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT2A receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT1A and 5-HT2A) and dopamine (D1 and D2) receptors. (R)-Roemerine and (+/-)-nuciferine were found to have high affinity for the 5-HT2A receptor (Ki = 62 and 139 nm, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT2A receptor over the 5-HT1A, D1 and D2 receptors. Investigation into the ligandreceptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipoledipole interactions with several of the key residues in the 5-HT2A receptor-binding site. |
| format | Article |
| id | my.um.eprints-8149 |
| institution | Universiti Malaya |
| publishDate | 2013 |
| record_format | eprints |
| spelling | my.um.eprints-81492013-07-22T01:06:46Z http://eprints.um.edu.my/8149/ Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity Munusamy, V. Yap, B.K. Buckle, M.J.C. Doughty, S.W. Chung, L.Y. R Medicine Selective blockade of the serotonin 5-HT2A receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT2A receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT1A and 5-HT2A) and dopamine (D1 and D2) receptors. (R)-Roemerine and (+/-)-nuciferine were found to have high affinity for the 5-HT2A receptor (Ki = 62 and 139 nm, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT2A receptor over the 5-HT1A, D1 and D2 receptors. Investigation into the ligandreceptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipoledipole interactions with several of the key residues in the 5-HT2A receptor-binding site. 2013 Article PeerReviewed Munusamy, V. and Yap, B.K. and Buckle, M.J.C. and Doughty, S.W. and Chung, L.Y. (2013) Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity. Chemical Biology & Drug Design, 81 (2). pp. 250-256. ISSN 1747-0277, DOI https://doi.org/10.1111/cbdd.12069 <https://doi.org/10.1111/cbdd.12069>. http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12069/abstract 10.1111/cbdd.12069 |
| spellingShingle | R Medicine Munusamy, V. Yap, B.K. Buckle, M.J.C. Doughty, S.W. Chung, L.Y. Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title | Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title_full | Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title_fullStr | Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title_full_unstemmed | Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title_short | Structure-based identification of aporphines with selective 5-HT2A receptor-binding activity |
| title_sort | structure-based identification of aporphines with selective 5-ht2a receptor-binding activity |
| topic | R Medicine |
| url | http://eprints.um.edu.my/8149/ http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12069/abstract |
| url_provider | http://eprints.um.edu.my/ |