Academic Journal
Synthesis, binding, and modeling studies of new cytisine derivatives, as ligands for neuronal nicotinic acetylcholine receptor subtypes
| العنوان: | Synthesis, binding, and modeling studies of new cytisine derivatives, as ligands for neuronal nicotinic acetylcholine receptor subtypes |
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| المؤلفون: | B. Tasso, C. Canu Boido, E. Terranova, C. Gotti, L. Riganti, R. Artali, F. Sparatore, F. Clementi, G. Bombieri, F. Meneghetti |
| المساهمون: | B. Tasso, C. Canu Boido, E. Terranova, C. Gotti, L. Riganti, F. Clementi, R. Artali, G. Bombieri, F. Meneghetti, F. Sparatore |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2009 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Settore CHIM/08 - Chimica Farmaceutica, Settore BIO/14 - Farmacologia |
| الوصف: | The availability of drug affecting neuronal nicotinic acetylcholine receptors (nAChRs) may have important therapeutic potential for the treatment of several CNS pathologies. Pursuing our efforts on the systematic structural modification of cytisine and N-arylalkyl and N-aroylalkyl cytisines were synthesized and tested for the displacement of [(3)H]-epibatidine and [(125)I]-alpha-bungarotoxin from the most widespread brain nAChRs subtypes alpha(4)beta(2) and alpha(7), respectively. While the affinity for alpha(7) subtype was rather poor (K(i) from 0.4 to >50 microM), the affinity for alpha(4)beta(2) subtype was very interesting, with nanomolar K(i) values for the best compounds. The N-substituted cytisines were docked into the rat and human alpha(4)beta(2) nAChR models based on the extracellular domain of a molluscan acetylcholine binding protein. The docking results agreed with the binding data, allowing the detection of discrete amino acid residues of the alpha and beta subunits essential for the ligand binding on rat and human nAChRs, providing a novel structural framework for the development of new alpha(4)beta(2) selective ligands. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/19548687; info:eu-repo/semantics/altIdentifier/wos/WOS:000268139900030; volume:52; issue:14; firstpage:4345; lastpage:4357; journal:JOURNAL OF MEDICINAL CHEMISTRY; http://hdl.handle.net/2434/67086; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-67650756936 |
| DOI: | 10.1021/jm900225j |
| الاتاحة: | http://hdl.handle.net/2434/67086 https://doi.org/10.1021/jm900225j |
| رقم الانضمام: | edsbas.54CFA76F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/jm900225j |
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