The Novel Arylamidine T-2307 Selectively Disrupts Yeast Mitochondrial Function by Inhibiting Respiratory Chain Complexes
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The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function.
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T-2307 has high selectivity for fungal mitochondria over mammalian cells.
“T-2307 has high selectivity for fungal mitochondria over mammalian cells, which makes it a potent drug candidate for fungal infection (34, 39).”
From Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review (2023) · cites this paper as [34]
T-2307 is effective against drug-resistant fungal isolates both in vitro and in vivo, including echinocandin-resistant C. albicans and Candida glabrata and azole-resistant C. albicans.
“Moreover, T-2307 is effective against drug-resistant fungal isolates both in vitro and in vivo, which highlights its potent antifungal activities against echinocandin-resistant C. albicans and Candida glabrata and azole-resistant C. albicans (29, 32–34).”
From Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review (2023) · cites this paper as [34]
ATI-2307 is a first-in-class arylamidine that disrupts yeast cellular respiration by inhibiting mitochondrial respiratory chain complexes III and IV.
“It is a first-in-class arylamidine with a novel antifungal mechanism: the disruption of yeast cellular respiration via inhibition of mitochondrial respiratory chain complexes III and IV.”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [85]
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“T-2307 has high selectivity for fungal mitochondria over mammalian cells, which makes it a potent drug candidate for fungal infection (34, 39).”
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Inhibitory effect of copper chelators on the budding in Candida albicans
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Mitochondria in Cryptococcus: an update of mitochondrial transcriptional regulation in Cryptococcus
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- Authors
- Yamashita, K., Miyazaki, T., Fukuda, Y., Mitsuyama, J., Saijo, T., Shimamura, S., Yamamoto, K., Imamura, Y., Izumikawa, K., Yanagihara, K., Kohno, S., & Mukae, H.
- Affiliations
- Fujifilm (Japan) (JP)
- Nagasaki University Hospital (JP)
- FUJIFILM Toyama Chemical Co., Ltd. (Japan) (JP)
- Nagasaki University (JP)
- Corresponding author
- Miyazaki, Taiga
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2019-08
- Volume
- 63
- Issue
- 8
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC6658782
- OpenAlex
- W2953380395
- Cited by
- 77
- References
- 39
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 14 · 2023: 10 · 2022: 11 · 2021: 13 · 2020: 7
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Nagasaki University's Academic Output SITE (Nagasaki University) (submittedVersion, cc-by-nc-nd)
- Funders
- Fujifilm Toyama Chemical Co., Ltd.
- Fujifilm Corporation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- arylamides, antifungal agents, respiratory chain complexes, complex III inhibition, complex IV inhibition, mitochondrial dysfunction, yeast mitochondria, intracellular ATP depletion, selective toxicity, fungal pathogens
- MeSH terms
- Adenosine Triphosphate, Amidines, Animals, Antifungal Agents, Candida albicans, Cattle, Microbial Sensitivity Tests, Mitochondria, Mitochondria, Heart, Mitochondria, Liver, NADH Dehydrogenase, Saccharomyces cerevisiae, Electron Transport Complex II, Electron Transport Complex I, Rats
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