title: Neuronal nicotinic receptor agonists: a multi-approach development of the pharmacophore.
abstract: Based on the results obtained with different automated computational approaches as applied to the study of eleven high-affinity agonists of the neuronal nicotine acetylcholine receptor (nAChR), belonging to different chemical classes, new relevant features were detected which complement the existing pharmacophores. Convergent results from DISCO (Distance Comparison), QXP (Quick Explore), Catalyst/HipHop, and MIPSIM (Molecular Interaction Potential Similarity) allowed us to identify and locate, in a well defined spatial arrangement, three geometrically independent key structural features: (i) a positively charged nitrogen atom for ionic or hydrogen bond interactions, (ii) a lone pair of the pyridine nitrogen or a specific lone pair of a carbonyl oxygen, as a hydrogen bond acceptor, and (iii) a centre of a hydrophobic area generally occupied by aliphatic cycles. The pharmacophore presented herein, along with predictive 2D and 3D QSAR models recently developed in our group, could represent valuable computational tools for the design of new nAChR agonists having therapeutical potential.
authors.affiliation: Dipartimento Farmacochimico, Università di Bari, ltaly.
authors.forename: O
authors.initials: O
authors.lastname: Nicolotti
authors.forename: M
authors.initials: M
authors.lastname: Pellegrini-Calace
authors.forename: A
authors.initials: A
authors.lastname: Carrieri
authors.forename: C
authors.initials: C
authors.lastname: Altomare
authors.forename: N B
authors.initials: NB
authors.lastname: Centeno
authors.forename: F
authors.initials: F
authors.lastname: Sanz
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000818:Animals; D003198:Computer Simulation; D015195:Drug Design; D066298:In Vitro Techniques; D008024:Ligands; D008956:Models, Chemical; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism
chemical_list: D008024:Ligands; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic