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

Journal of the Serbian Chemical Society

关键词: malaria;    artemisinin;    molecular docking;    MEP Maps;    QSAR;   

DOI  :  10.2298/JSC100126124F

来源: DOAJ

【 摘 要 】

Artemisinin and 18 derivatives with antimalarial activity against W-2 strainsof Plasmodium falciparum were studied through quantum chemistry andmultivariate analysis. The geometry optimization of the structures wasrealized with the Hartree-Fock (HF) theory and 3-21G basis set. Maps ofmolecular electrostatic potential (MEP) and molecular docking were used toinvestigate 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. Apredictive model was generated by the Partial Least Square (PLS) methodthrough 15 molecules and 4 used as an external validation set, which wereselected in the training set, the validation parameters of which are Q2 =0.85 and R2 = 0.86. The model included as molecular parameters, the radialdistribution function, RDF060e, the hydration energy, HE, and the distancebetween 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 mapsand the PLS analysis.

【 授权许可】

Unknown