Vismione H and structurally related anthranoid compounds of natural and synthetic origin as promising drugs against the human malaria parasite Plasmodium falciparum: structure-activity relationships.

Natural and synthetic anthranoid compounds were subjected to an evaluation against asexual erythrocytic stages of the human malaria parasite Plasmodium falciparum in vitro. Stimulated by the good activities of Vismia guineënsis extracts, a more detailed investigation of the active principles revealed the pre-nylated preanthraquinone vismione H (1) to be a potent antimalarial [50% growth-inhibitory concentration (IC50) 0.088 microg/ml]. On the basis of this finding a series of chemically related phlegmacins (2-5), flavomannins (6-8), and rufoolivacins (9-11) isolated from several species of Cortinarius, a genus of higher fungi, and 5 synthetic vismione-like anthranoids (12-16) were evaluated as well. Although these compounds displayed weaker antiplasmodial effects than did vismione H (1) itself, considerable levels of activity were obtained with phlegmacin B1 (2), flavomannin-6,6'-di-O-methyl ether A1 (6), trans-4-hydroxy-flavomannin-6,6'-di-O-methyl ether A (8), and rufoolivacin B (10). Initial preconditions for activity within the vismiones and related anthranoids were established.