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A study of new antimalarial artemisinins through molecular modeling and multivariate analysis

Author(s): Ferreira João E.V. | Figueiredo Antonio F. | Barbosa Jardel P. | Cristino Maria G.G. | Macedo Williams J.C. | Silva Osmarina P.P. | Malheiros Bruno V. | Serra Raymony T.A. | Ciriaco-Pinheiro Jose

Journal: Journal of the Serbian Chemical Society
ISSN 0352-5139

Volume: 75;
Issue: 11;
Start page: 1533;
Date: 2010;
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Keywords: malaria | artemisinin | molecular docking | MEP Maps | QSAR

Artemisinin and 18 derivatives with antimalarial activity against W-2 strains of Plasmodium falciparum were studied through quantum chemistry and multivariate analysis. The geometry optimization of the structures was realized with the Hartree-Fock (HF) theory and 3-21G basis set. Maps of molecular electrostatic potential (MEP) and molecular docking were used to investigate the interaction between the ligands and the receptor (heme). Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were employed to select the most important descriptors related to activity. A predictive model was generated by the Partial Least Square (PLS) method through 15 molecules and 4 used as an external validation set, which were selected in the training set, the validation parameters of which are Q2 = 0.85 and R2 = 0.86. The model included as molecular parameters, the radial distribution function, RDF060e, the hydration energy, HE, and the distance between the O1 atom from the ligand and the iron atom from heme, d(Fe-O1). Thus, the synthesis of new derivatives may follow the results of the MEP maps and the PLS analysis.

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