title: Getting new bronchodilator compounds from molecular topology.
abstract: Molecular topology has been used to select new lead bronchodilator compounds. The main advantage of this method, as compared to others frequently used, is that it does not require a previous explicit knowledge of the mechanism of action (MOA) of the compounds analyzed. A large database (12,000 chemicals) has been examined in this study to find less than 5% compounds with bronchodilator activity. After removing those compounds already described as bronchodilators, we present here the results for 20 among these compounds, some of them showing other pharmacological activities. Some of the compounds selected in this study showed higher relaxation and higher potency than theophylline, which is the reference drug used in the bronchodilator assay performed. For instance, tetrahydro-papaveroline showed significantly higher values than theophylline (93.9% versus 77.0% and pD2=7.30 versus pD2=4.69, respectively). Other compounds, although eliciting small or no relaxation at 0.1mM, produced larger relaxation at higher concentrations (1mM). In conclusion, the molecular topology based approach used in this work has demonstrated to be effective in the search of new bronchodilators.
authors.affiliation: Unidad de Investigación de Diseño de Fármacos y Conectividad Molecular, Departamento de Quimica-Física, Facultat de Farmàcia, Universitat de València, 46100 Burjasot, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ríos-Santamarina
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Domenech
authors.forename: Jorge
authors.initials: J
authors.lastname: Gálvez
authors.forename: Jesús
authors.initials: J
authors.lastname: Morcillo Esteban
authors.forename: Pedro
authors.initials: P
authors.lastname: Santamaría
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D001993:Bronchodilator Agents / Q000737:chemistry*; D004610:Ellagic Acid / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D008962:Models, Theoretical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000737:chemistry
chemical_list: D001993:Bronchodilator Agents; D007211:Indoles; D004610:Ellagic Acid; D013806:Theophylline