Electrochemical behavior of indolone-N-oxides: Relationship to structure and antiplasmodial activity

Abstract Indolone- N -oxides exert high parasiticidal activity at the nanomolar level in vitro against Plasmodium falciparum , the parasite responsible for malaria. The bioreductive character of these molecules was investigated using cyclic voltammetry and EPR spectroelectrochemistry to examine the relationship between electrochemical behavior and antimalarial activity and to understand their mechanisms of action. For all the compounds (37 compounds) studied, the voltammograms recorded in acetonitrile showed a well-defined and reversible redox couple followed by a second complicated electron transfer. The first reduction (− 0.88 V  E 1/2 N -oxide function to form a radical nitroxide anion. The second reduction (− 1.65 V  E 1/2 N -oxide structure can be established for compounds with R 1  = ―OCH 3 , R 2  = H, and electron-withdrawing substituents on the phenyl group at R 3 . The results help in the design of new molecules with more potent in vivo antimalarial activity.