title: Ligand based validated comparative chemometric modeling and pharmacophore mapping of aurone derivatives as antimalarial agents.
abstract: Chloroquine resistance is nowadays a great problem. Aurone derivatives are effective against chloroquine resistant parasite. Ligand based validated comparative chemometric modeling through 2D-QSAR and kNN-MFA 3DQSAR studies as well as common feature 3D pharmacophore mapping were done on thirtyfive aurone derivatives having antimalarial activity. Statistically significant 2D-QSAR models were generated on unsplitted as well as splitted dataset by MLR and PLS technique. The MLR model of the unsplitted method was validated by two-deep cross validation and 10 fold cross validation for determining the predictive ability. The PLS technique of the unsplitted method was done to compare the significance of these methods. In the splitted method, model was developed on the training set by Y-based ranking method by using the same descriptors and was validated on fifty pairs of the test and the training sets by k-MCA technique. These models generated by using the same descriptors were well validated irrespective of MLR as well as PLS analysis of unsplitted as well as splitted methods and are showing similar results. Therefore, these descriptors and model generated were reliable and robust. The kNN-MFA 3D-QSAR models were generated by three variable selection methods: genetic algorithm, simulated annealing and stepwise regression. The kNN-MFA 3D-QSAR results support the 2D QSAR data and in turn validate the earlier observed SAR results. Common feature 3D-pharmacophore generation was performed on these compounds to validate both 2D and 3D-QSAR studies as well as the earlier observed SAR data. The work highlights the required structural features for the higher antimalarial activity.
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box-17020, Jadavpur University, Kolkata-700032, India.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Adhikari
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Halder
authors.forename: Chanchal
authors.initials: C
authors.lastname: Mondal
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
mesh_terms: D000465:Algorithms; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology*; D017076:Computer-Aided Design; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008288:Malaria / Q000188:drug therapy; D008958:Models, Molecular; D010961:Plasmodium / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001572:Benzofurans; D008024:Ligands; C486837:aurone