Aminonaphthoquinones--a novel class of compounds with potent antimalarial activity against Plasmodium falciparum.

Malaria is a major tropical disease, which kills two million people annually. The population at risk from this disease has increased because of the difficulties in eradicating the mosquito vector in the endemic regions and the emergence and spread of parasite resistance to all the commonly used antimalarials. Since antimalarials are the major arsenal for treatment of the disease, there is an urgent need for newer drugs with novel mechanisms of action, which will be effective against all strains of the parasite. As a part of our anti-infective drug discovery program, we have investigated 18 compounds including several synthetic and natural naphthoquinones as potential antimalarial agents. We have identified aminonaphthoquinones, as a class of antimalarial compounds with antimalarial activity against Plasmodium falciparum. Among these compounds, 2-amino-3-chloro-1,4-naphthoquinone is the most potent. It had an IC(50)of 0.18 micro M (37.3 ng ml(-1)) against the W2 clone, and is more potent than chloroquine, which had an IC(50)of 0.23 micro M (72 ng ml(-1)). It was also active against the D6 clone. In general, 2-amino-1,4-naphthoquinone analogs and the 4-amino-1,2-napthoquinone analog showed promising antimalarial activity in the bioassay. In contrast, a number of 2-hydroxy-1,4-naphthoquinones and dimeric quinones were less active. Copyright 2001 Academic Press.