title: Pharmacophore mapping of arylamino-substituted benzo[b]thiophenes as free radical scavengers.
abstract: Predictive pharmacophore models have been developed for a series of arylamino-substituted benzo[b]thiophenes exhibiting free radical scavenging activity. 3D pharmacophore models were generated using a set of 20 training set compounds and subsequently validated by mapping 6 test set compounds using Discovery Studio 2.1 software. Further model validation was performed by randomizing the data using Fischer's validation technique at the 95% confidence level. The most predictive pharmacophore model developed using the conformers obtained from the BEST method showed a correlation coefficient (r) of 0.942 and consisted of three features: hydrogen bond donor, hydrogen bond acceptor and aromatic ring. Acceptable values of external validation parameters, like R2pred (0.853) and r2m(test) (0.844), also implied that the external predictivity of the model was significant. The development of further pharmacophore models using conformers obtained from the FAST method yielded a few models with good predictivity, with the best one (r=0.904) consisting of two features: hydrogen bond donor and hydrogen bond acceptor. Significant values of external validation parameters, R2pred (0.913) and r2m(test) (0.821), also reflect the high predictive ability of the model. Again, Fischer validation results implied that the models developed were robust enough and their good results were not based on mere chance. These validation approaches indicate the reliability of the predictive abilities of the 3D pharmacophore models developed here, which may thus be further utilized as a 3D query tool in the virtual screening of new chemical entities with potent antioxidant activities.
authors.affiliation: Drug Theoretics and Cheminformatics Lab, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India.
authors.forename: Indrani
authors.initials: I
authors.lastname: Mitra
authors.forename: Achintya
authors.initials: A
authors.lastname: Saha
authors.forename: Kunal
authors.initials: K
authors.lastname: Roy
mesh_terms: D019295:Computational Biology; D016166:Free Radical Scavengers / Q000737:chemistry*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D016166:Free Radical Scavengers; D013876:Thiophenes; C088015:benzothiophene