Antimalarial and Anticancer Activity Evaluation of Bridged Ozonides, Aminoperoxides, and Tetraoxanes

Bridged aminoperoxides, for the first time, were investigated for the in vitro antimalarial activity against the chloroquine-resistant Plasmodium falciparum strain K1 and for their cytotoxic activities against immortalized human normal liver (LO2) and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer cell lines. Aminoperoxides exhibit good cytotoxicity against lung A549 cancer cell line. Synthetic ozonides were shown to have high activity against the chloroquine-resistant P. falciparum. A cyclic voltammetry study of peroxides was performed, and most of the compounds did not show a direct correlation in oxidative capacity-activity. Peroxides were analyzed for ROS production to understand their mechanism of action. However, none of the compounds has an impact on ROS generation, suggesting that ozonides induce apoptosis in HepG2 cells through ROS-independent dysfunction pathway.

Automated summary

In this study, the in vitro activities of bridged aminoperoxides against chloroquine-resistant Plasmodium falciparum and human cancer cells were investigated. The results showed that aminoperoxides exhibited good cytotoxicity against lung cancer cells, while synthetic ozonides displayed high activity against chloroquine-resistant P. falciparum. Moreover, the oxidative capacity of the compounds did not directly correlate with their activity, and the ozonides induced apoptosis in liver cancer cells through a ROS-independent dysfunction pathway.