A study of new antimalarial artemisinins through molecular modeling and multivariate analysis
| Autor: | José Ciríaco-Pinheiro, Maria da Gloria Gomes Cristino, Bruno Veiga Malheiros, Raymony Tayllon Alves Serra, João E. V. Ferreira, Osmarina P. P. Silva, Jardel Pinto Barbosa, Antonio Florêncio de Figueiredo, Williams J. C. Macedo |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Quantitative structure–activity relationship
Molecular model Chemistry QSAR malaria Atom (order theory) General Chemistry molecular docking Energy minimization MEP Maps Hierarchical clustering lcsh:Chemistry artemisinin lcsh:QD1-999 Computational chemistry Principal component analysis Molecule Basis set |
| Zdroj: | Journal of the Serbian Chemical Society, Vol 75, Iss 11, Pp 1533-1548 (2010) |
| ISSN: | 0352-5139 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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