title: From Molecular Docking to 3D-Quantitative Structure-Activity Relationships (3D-QSAR): Insights into the Binding Mode of 5-Lipoxygenase Inhibitors.
abstract: Pharmacological intervention with 5-Lipoxygenase (5-LO) is a promising strategy for treatment of inflammatory and allergic ailments, including asthma. With the aim of developing predictive models of 5-LO affinity and gaining insights into the molecular basis of ligand-target interaction, we herein describe QSAR studies of 59 diverse nonredox-competitive 5-LO inhibitors based on the use of molecular shape descriptors and docking experiments. These studies have successfully yielded a predictive model able to explain much of the variance in the activity of the training set compounds while predicting satisfactorily the 5-LO inhibitory activity of an external test set of compounds. The inspection of the selected variables in the QSAR equation unveils the importance of specific interactions which are observed from docking experiments. Collectively, these results may be used to design novel potent and selective nonredox 5-LO inhibitors.
authors.affiliation: Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06330 Ankara, Turkey tel.: +90-312-2023236; fax: +90-312-2235018.
authors.forename: Gokcen
authors.initials: G
authors.lastname: Eren
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo 1, 06123 Perugia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
authors.affiliation: Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 06330 Ankara, Turkey tel.: +90-312-2023236; fax: +90-312-2235018. banoglu@gazi.edu.tr.
authors.forename: Erden
authors.initials: E
authors.lastname: Banoglu
keywords: 3D-QSAR; 5-LO; Molecular docking; Nonredox 5-LO inhibitor