A Quantitative Structure-Activity Relationship Study on the Antimalarial Activities of 4-Aminoquinoline, Febrifugine and Artemisinin Compounds

Abstract

Quantum chemical molecular descriptors representing different types of chemical reactivity were employed to investigate the antimalarial activities of 4-aminoquinoline, febrifugine, artemisinin and their derivatives. The quantitative structure-activity relationship results reveal that: (i) the antimalarial activities of 4-aminoquinoline compounds against the chloroquine-sensitive Plasmodium falciparum 3D7 strain are mainly affected by the electron flow and polarization interactions; (ii) The reactivity descriptors for the activities of febrifugine compounds against the chloroquine-resistant Plasmodium falciparum FCR-3 strain are the electron-acceptance chemical potential, the maximum nucleophilic and electrophilic local softness, the maximum positive charge of the hydrogen atom, etc.; (iii) The electron-donation chemical potential, the maximum negative charge, the inverse of the apolar surface area and the molar volume of artemisinin compounds are the most important descriptors for evaluating the activity against the chloroquine-resistant Plasmodium falciparum W-2 strain.