Synthetic alkyl substituted quinones oxidize membrane proteins and arrest Plasmodium falciparum growth in vitro

Quinones are a family of bioactive compounds with known antibacterial, antiviral and antiparasitic activity. The capacity of quinoid compounds to accept electrons, due to electron-attracting (or donating) substituents at the quinone moiety, modulates their redox activity upon interaction with biological systems. Nine quinone derivate including three 2 - hydroxyl - 1, 4 - naphthoquinone; three 4,5 - and three 4,9 - naphthoquinone scaffolds, were synthesized and evaluated against 3D7 and Dd2 Plasmodium falciparum strains and evaluated the oxidative stress. Cell viability was determined MTT-related colorimetric assay (EZ4u; Biomedical, Austria). Selectivity of these compounds was evaluated by comparing in vitro, of cytotoxicity in human fibroblast and antimalarial activity in Plasmodium falciparum. Peripheral blood mononuclear cells and hemoglobin release from human erythrocytes were evaluated too. Antiplasmodial activity was evaluated by fluorometry methods. In addition, oxidized membrane protein in the malaria parasite was evaluated in vitro by derivatization, after treatment at IC50 values on P. falciparum Dd2 strain. Quinones showed IC50 values in the micromole range, selectivity indexes for quinones was variable, compounds 2 and 3 showed excellent selectivity. In vitro antiplasmodial activity was showed; this result is an incentive to continue synthesis and studying the quinoid compounds. Key words: Malaria, Quinones, Plasmodium falciparum.