Bajsa J, Singh K, Nanayakkara D, Duke SO, Rimando AM, Evidente
A, Tekwani BL.A survey of synthetic and natural phytotoxic
compounds and phytoalexins as potential antimalarial compounds.
Biol Pharm Bull. 2007 Sep;30(9):1740-4.
National Center for Natural Products Research, School of
Pharmacy, University of Mississippi, MS 38677, U.S.A.
jbajsa@olemiss.edu
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.
PMID: 17827731 |
