Metacytofilin has potent anti-malarial activity

Metacytofilin (MCF) was isolated from the fungus Metarhizium sp. TA2759. Although MCF possesses anti-Toxoplasma activity, the effects of this compound against other parasites are unknown. Here, we evaluated the in vitro anti-malarial activity of MCF against the 3D7 strain and the chloroquine-resista...

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Published in:Parasitology international 2021-04, Vol.81, p.102267-102267, Article 102267
Main Authors: Leesombun, Arpron, Iijima, Masatomi, Pagmadulam, Baldorj, Orkhon, Banzragchgarav, Doi, Hiroyasu, Issiki, Kunio, Sawa, Ryuichi, Nihei, Coh-ichi, Nishikawa, Yoshifumi
Format: Article
Language:English
Subjects:
Chloroquine resistance
Malaria
Metacytofilin
Plasmodium falciparum
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Summary:Metacytofilin (MCF) was isolated from the fungus Metarhizium sp. TA2759. Although MCF possesses anti-Toxoplasma activity, the effects of this compound against other parasites are unknown. Here, we evaluated the in vitro anti-malarial activity of MCF against the 3D7 strain and the chloroquine-resistant K1 strain of Plasmodium falciparum. The half maximal inhibitory concentrations (IC50) of MCF against the 3D7 and K-1 strains following culture for 48 h were 666 nM and 605 nM, respectively. Artemisinin was more potent than MCF against both strains (3D7 IC50: 17.4 nM; K-1 IC50: 18.3 nM), while chloroquine was ineffective against the chloroquine-resistant strain (3D7 IC50: 39.1 nM; K-1 IC50: 1.62 μM). MCF affected the ring stage of the parasites, resulting in their death as shown by spots within red blood cells. MCF also inhibited parasite growth following culture for 72 h (3D7 IC50, 285 nM). Four optical isomers of cyclo[Leu-Phe]-diketopiperazine derivatives with modified methoxy and/or hydroxyl groups lost anti-malarial activity, suggesting that the spatial positions of the methoxy and hydroxyl groups in MCF play an important role in its anti-malarial effects. Together, these data suggest that MCF may represent a promising lead compound for treatment of drug-resistant malarial parasites. [Display omitted] •Metacytofilin (MCF) was isolated from Metarhizium sp. fungi.•MCF showed activity against both chloroquine-sensitive and -resistant strains.•MCF affected the parasite ring stage.•MCF is a potent hit compound and a potential anti-malarial drug.
ISSN:1383-5769
1873-0329
DOI:10.1016/j.parint.2020.102267