Artemisinin form the most important class of antimalarial agents currently available, and is a unique
sesquiterpene peroxide occurring as a constituent of Artemisia annua. Artemisinin is effectively used in the treatment of
drug-resistant Plasmodium falciparum and because of its rapid clearance of cerebral malaria, many clinically useful
semisynthetic drugs for severe and complicated malaria have been developed. However, one of the major disadvantages
of using artemisinins is their poor solubility either in oil or water and therefore, in order to overcome this difficulty many
derivatives of artemisinin were prepared. A comparative study on the chemical reactivity of artemisinin and some of its
derivatives is performed using density functional theory (DFT) calculations. DFT based global and local reactivity
descriptors, such as hardness, chemical potential, electrophilicity index, Fukui function, and local philicity calculated at
the optimized geometries are used to investigate the usefulness of these descriptors for understanding the reactive nature
and reactive sites of the molecules. Multiple regression analysis is applied to build up a quantitative structure-activity
relationship (QSAR) model based on the DFT based descriptors against the chloroquine-resistant, mefloquine-sensitive
Plasmodium falciparum W-2 clone.
Keywords: Artemisinin, DFT, electrophilicity index (ω), Fukui function (FF), hardness (η), QSAR.
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