Discovery of an antimalarial compound, burnettiene A, with a multidrug-sensitive Saccharomyces cerevisiae screening system based on mitochondrial function inhibitory activity

ABSTRACT In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natur...

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Published in:Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2024-08
Main Authors: Kimishima, Aoi, Nishitomi, Atsuka, Tsuruoka, Iori, Sakai, Katsuyuki, Hokari, Rei, Honsho, Masako, Honma, Sota, Ono, Yuki, Kondo, Naozumi, Tsutsumi, Hayama, Kikuchi, Yuta, Tokiwa, Toshiyuki, Kojima, Hiroki, Higo, Mayuka, Nonaka, Kenichi, Inahashi, Yuki, Iwatsuki, Masato, Fuji, Shin-ichi, Jang, Jun-Pil, Jang, Jae-Hyuk, Chinen, Takumi, Usui, Takeo, Asami, Yukihiro
Format: Article
Language:English
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Summary:ABSTRACT In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1, we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates.
ISSN:1347-6947
1347-6947
DOI:10.1093/bbb/zbae098