Antimalarial screening was performed for microbial metabolites that simulate
artemisinin in their mode of action, a potent
antimalarial component of an herbal remedy with a characteristic
peroxide structure.
Nanaomycin A was identified in this screen as an
antimalarial compound, together with
radicicol and several other compounds already reported (J.
Antibiotics 51: 153 approximately 160, 1998).
Nanaomycin A inhibited in vitro growth of the human
malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as
radicicol and about 1/10 as potent as
artemisinin. Studies on the mode of action suggested that the
antimalarial action of the two non-
peroxides,
nanaomycin A and
radicicol, involved
heme-dependent radical generation, as is for the
peroxide artemisinin. Namely, the inhibition of in vitro growth of
malaria parasite by
nanaomycin A or
radicicol was reversed by
tocopherol, a radical scavenger added to the assay mixture. Secondly, in a reaction system established for radical detection, in which a test radical donor and
beta-alanylhistidine as a radical recipient were incubated with and without
hemin, the two compounds caused
heme-dependent decreases of
beta-alanylhistidine, as did
artemisinin. Among the 14 microbial metabolites identified during this screening, a correlation was observed between
antimalarial activity and
heme-dependent radical generating activity.