Design of novel α7-subtype-preferring nicotinic acetylcholine receptor agonists: application of docking and MM-PBSA computational approaches, synthetic and pharmacological studies
Articolo
Data di Pubblicazione:
2009
Citazione:
Design of novel α7-subtype-preferring nicotinic acetylcholine receptor agonists: application of docking and MM-PBSA computational approaches, synthetic and pharmacological studies / G. Grazioso, D.Y. Pomè, C. Matera, F. Frigerio, L. Pucci, C. Gotti, C. Dallanoce, M. De Amici. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 19:22(2009), pp. 6353-6357. [10.1016/j.bmcl.2009.09.073]
Abstract:
In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric α7 channels, we carried out the virtual screening of a test set of potential nicotinic ligands, and adopted a simplified MM-PBSA approach to estimate their relative binding free energy values. By means of this procedure, previously validated by a training set of compounds, we reached a realistic compromise between computational accuracy and calculation rate, and singled out a small group of novel structurally related derivatives characterized by a promising theoretical affinity for the α7 subtype. Among them, five new compounds were synthesized and assayed in binding experiments at neuronal α7 as well as α4β2 nAChRs.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
MM-PBSA; Neuronal nicotinic acetylcholine receptors; alpha 7 Selective nicotinic agonists; Binding affinity
Elenco autori:
G. Grazioso, D.Y. Pomè, C. Matera, F. Frigerio, L. Pucci, C. Gotti, C. Dallanoce, M. De Amici
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