In the search for nicotinic acetylcholine receptor (nAChRs) agonists with a selective affinity for the homomeric alpha7 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 alpha7 subtype. Among them, five new compounds were synthesized and assayed in binding experiments at neuronal alpha7 as well as alpha4beta2 nAChRs.
        
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Grazioso G, Pome DY, Matera C, Frigerio F, Pucci L, Gotti C, Dallanoce C, De Amici M (2009) Design of novel alpha7-subtype-preferring nicotinic acetylcholine receptor agonists: application of docking and MM-PBSA computational approaches, synthetic and pharmacological studies Bioorganic & Medicinal Chemistry Lett19: 6353-7