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

Year: 2024
Type: article
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.
DOI: 10.1093/bbb/zbae098
Authors: Aoi Kimishima, Atsuka Nishitomi, Iori Tsuruoka, Katsuyuki Sakai, Rei Hokari, Masako Honsho, Sota Honma, Yuki Ono, Naozumi Kondo, Hayama Tsutsumi, Yuta Kikuchi, Toshiyuki Tokiwa, Hiroki Kojima, Mayuka Higo, Kenichi Nonaka, Yuki Inahashi, Masato Iwatsuki, Shin-ichi Fuji, Jun-Pil Jang, Jae-Hyuk Jang, Takumi Chinen, Takeo Usui, Yukihiro Asami
Institutions: Ōmura Satoshi Memorial Institute, Kitasato University, Akita Prefectural University, Korea Research Institute of Bioscience and Biotechnology, The University of Tokyo, University of Tsukuba
Language: English
Open Access status: bronze
Funders: Japan Agency for Medical Research and Development, Macquarie University, Ministry of Education, Korea Research Institute of Bioscience and Biotechnology, Kitasato University, Ministry of Science and ICT, South Korea, Japan Society for the Promotion of Science, RIKEN
Awards: G1191154095, G1384871578, Search for novel plant immune-priming compounds by simple screening system using nitric oxide, G2643849817, G4081873599, G6377000219, Discovery of microorganism-derived anti-MRSA therapeutic seed compounds that inhibit drug resistance factors, G6670503325
OpenAlex ID: W4400514575
FWCI:
Cites: 17
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Related to: 10