Activities of new acridone alkaloid derivatives against Plasmodium yoelii in vitro.

Forty-seven new acridone alkaloid derivatives (SA compounds) were tested for antimalarial activity in vitro. At a concentration of 1.0 microgram/ml, six of these inhibited 50% or more of the incorporation of [3H]hypoxanthine into Plasmodium yoelii in vitro. The four most potent compounds, SA 3757, SA 3548, SA 3761 and SA 3499, showed 50% inhibitory concentration (IC50) values of 0.023 microgram/ml, 0.03 microgram/ml, 0.053 microgram/ml and 0.15 microgram/ml, respectively. The chemotherapeutic indexes of these four acridones, based on the ratio of the 50% lethal concentration (LC50) values for cell growth of L1210 cells to the IC50 for inhibition of uptake of [3H]hypoxanthine into P. yoelii, were calculated to be equal to or more higher (greater than 870, 263, 189 and greater than 133, respectively) than chloroquine diphosphate (315) or pyrimethamine (87).