Aminonaphthoquinones - A novel class of compounds with potent antimalarialactivity against Plasmodium falciparum

Malaria is a major tropical disease, which kills two million people annuall y. The population at risk from this disease has increased because of the di fficulties in eradicating the mosquito vector in the endemic regions and th e emergence and spread of parasite resistance to all the commonly used anti malarials. Since antimalarials are the major arsenal for treatment of the d isease, there is an urgent need for newer drugs with novel mechanisms of ac tion, which will be effective against all strains of the parasite. As a par t of our anti-infective drug discovery program, we have investigated 18 com pounds including several synthetic and natural naphthoquinones as potential antimalarial agents. We have identified aminonaphthoquinones. as a class o f antimalarial compounds with antimalarial activity against Plasmodium falc iparum. Among these compounds, 2-amino-3-chlorol-1,4-naphthoquinone is the most potent. It had an IC50 of 0.18 muM (37.3 ng ml(-1)) against the W2 clo ne, and is more potent than chloroquine, which had an IC50 of 0.23 muM (72 ng ml(-1)). It was also active against the D6 clone, In general, 2-amino-1, 4-naphthoquinone analogs and the 3-amino-1,2-napthoquinone analog showed pr omising antimalarial activity in the bioassay. In contrast, a number of 2-h ydroxy-1,4-naphthoquinones and dimeric quinones were less active. (C) 2001 Academic Press.