A survey of synthetic and natural phytotoxic compounds and phytoalexins as potential antimalarial compounds.

The apicomplexan parasites pathogens such as Plasmodium spp. possess an apicoplast, a plastid organelle similar to those of plants. The apicoplast has some essential plant-like metabolic pathways and processes, making these parasites susceptible to inhibitors of these functions. The main objective of this paper is to det. if phytotoxins with plastid target sites are more likely to be good antiplasmodial compds. than are those with other modes of action. The antiplasmodial activities of some compds. with established phytotoxic action were detd. in vitro on a chloroquine (CQ) sensitive (D6, Sierra Leone) strain of Plasmodium falciparum. In this study, we provide in vitro activities of almost 50 such compds., as well as a few phytoalexins against P. falciparum. Endothall, anisomycin, and cerulenin had sufficient antiplasmodial action to be considered as new lead antimalarial structures. Some derivs. of fusicoccin possessed markedly improved antiplasmodial action than the parent compd. Our results suggest that phytotoxins with plastid targets may not necessarily be better antiplasmodials than those that act at other mol. sites. The herbicides, phytotoxins and the phytoalexins reported here with significant antiplasmodial activity may be useful probes for identification of new antimalarial drug targets and may also be used as new lead structures for new antiplasmodial drug discovery.