In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A-C, produced by Penicillium sp. FKI-4410.
In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A-C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC(50) values of 0.01 μg ml(-1) against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC(50) value of 57.2 μg ml(-1). The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.
Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
Masato
M
Iwatsuki
Shohei
S
Takada
Mihoko
M
Mori
Aki
A
Ishiyama
Miyuki
M
Namatame
Aki
A
Nishihara-Tsukashima
Kenichi
K
Nonaka
Rokuro
R
Masuma
Kazuhiko
K
Otoguro
Kazuro
K
Shiomi
Satoshi
S
Omura
D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010407:Penicillium / Q000378:metabolism*; D010962:Plasmodium berghei / Q000472:pathogenicity; D010963:Plasmodium falciparum / Q000187:drug effects*; D016896:Treatment Outcome
D000962:Antimalarials