title: Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.
abstract: Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, Parco Area delle 27/A, I-43100 Parma. marco.mor@unipr.it
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.forename: Silvia
authors.initials: S
authors.lastname: Rivara
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.forename: Simone
authors.initials: S
authors.lastname: Lorenzi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bordi
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Plazzi
authors.forename: Gilberto
authors.initials: G
authors.lastname: Spadoni
authors.forename: Annalida
authors.initials: A
authors.lastname: Bedini
authors.forename: Andrea
authors.initials: A
authors.lastname: Duranti
authors.forename: Andrea
authors.initials: A
authors.lastname: Tontini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Tarzia
mesh_terms: D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D044094:Receptors, Melatonin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D044094:Receptors, Melatonin