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 determine if phytotoxins with plastid target sites are more likely to be good antiplasmodial compounds than are those with other modes of action. The antiplasmodial activities of some compounds with established phytotoxic action were determined 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 compounds, 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 derivatives of fusicoccin possessed markedly improved antiplasmodial action than the parent compound. Our results suggest that phytotoxins with plastid targets may not necessarily be better antiplasmodials than those that act at other molecular 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.
Bajsa
Joanna
J
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, MS 38677, U.S.A. jbajsa@olemiss.edu
Singh
Kshipra
K
Nanayakkara
Dhammika
D
Duke
Stephen Oscar
SO
Rimando
Agnes Mamaril
AM
Evidente
Antonio
A
Tekwani
Babu Lal
BL
D000818:Animals; D000962:Antimalarials; D029681:Arabidopsis Proteins / Q000378:metabolism; D015195:Drug Design; D006540:Herbicides / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D018087:Plastids / Q000187:drug effects; D012717:Sesquiterpenes; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D000094162:Phytoalexins