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 Plasmodiu m falciparum in vitro. Stimulated by the good activities of Vismia guineens is extracts, a more detailed investigation of the active principles reveale d the prenylated preanthraquinone vismione H (1) to be a potent antimalaria l [50% growth-inhibitory concentration (IC50) 0.088 mu g/ml]. On the basis of this finding a series of chemically related phlegmacins (2-5), flavomann ins (6-8), and rufoolivacins (9-11) isolated from several species of Cortin arius, a genus of higher fungi, and 5 synthetic vismione-like anthranoids ( 12-16) were evaluated as well, Although these compounds displayed weaker an tiplasmodial effects than did vismione H (1) itself, considerable levels of activity were obtained with phlegmacin B-1 (2), flavomannin-6,6'-di-O-meth yl ether A(1) (6), trans-4-hydroxy-flavomannin-6, 6'-di-O-methyl ether A (8 ), and rufoolivacin B (10). Initial preconditions for activity within the v ismiones and related anthranoids were established.