Efficacy, Structure–Activity Relationship, and Mode of Action Studies of a New Generation of Acridine/Acridone-Based Antimalarials

Malaria continues to devastate humanity with significant global morbidity and mortality. The emerging resistance to antimalarials suggests artemisinin and its derivatives will encounter the same challenges as other antimalarial drugs. Strategies to accelerate developing new antimalarials include utilizing known scaffolds and making structural modifications to enhance properties and elucidate their mode of action. We have focused on acridine derivatives and describe 18 acridine/acridone analogs based on pyronaridine or quinacrine cores. Several molecules demonstrated potent