Ufisonitriles A and B, Antimalarial Isonitriles with Mitochondrial Function Inhibitory Activity Produced by <i>Amycolatopsis</i> sp. OK19-0009
Two novel antimalarials, named ufisonitriles A (<b>1</b>) and B (<b>2</b>), were isolated by bioassay-guided fractionation on mitochondrial function inhibitory activity using multidrug-sensitive budding yeast from the cultured broth of the Okinawan rare actinomycete <i>Amycolatopsis</i> sp. OK19-0009 strain. Their structures were comprehensively elucidated using HR-ESI-MS and 1D/2D NMR analyses and the modified Mosher's method. Structurally, <b>1</b> and <b>2</b> possess a novel skeleton with an isocyano group. <i>In vitro</i> antimalarial evaluation against <i>Plasmodium falciparum</i> strains revealed that <b>1</b> and <b>2</b> exhibited moderate activity with IC<sub>50</sub> values ranging from 28.6 to 1.12 μM. Furthermore, <b>1</b> and <b>2</b> reduced the malaria parasites by approximately 45% <i>in vivo</i> on intraperitoneal administration (30 mg/kg/day for 4 days) with no observed toxicity. We also provide a plausible biosynthesis pathway based on the genome sequence analysis.
Authors
- Takeo Usui (ORCID: https://orcid.org/0000-0003-2377-7499)
- Yoshihiro Watanabe (ORCID: https://orcid.org/0000-0002-5756-0530)
- Takumi Chinen (ORCID: https://orcid.org/0000-0001-9836-8839)
- Hiroki Kanto
- Takahiro Ishii (ORCID: https://orcid.org/0000-0003-4180-9917)
- Rei Hokari (ORCID: https://orcid.org/0000-0002-6091-0503)
- Akari Ikeda (ORCID: https://orcid.org/0000-0003-1374-6226)
- Yuki Inahashi (ORCID: https://orcid.org/0000-0001-7436-2037)
- Masato Iwatsuki (ORCID: https://orcid.org/0000-0001-8373-4314)
- Emi Arakawa
- A Take (ORCID: https://orcid.org/0000-0003-4056-5674)
- Toshiaki Teruya (ORCID: https://orcid.org/0000-0002-7018-7734)
- Yukihiro Asami (ORCID: https://orcid.org/0000-0003-1821-9169)
- Hideaki Hanaki (ORCID: https://orcid.org/0009-0006-7902-2414)
- Aki Ishiyama (ORCID: https://orcid.org/0000-0003-4703-8834)
- Tomoyasu Hirose (ORCID: https://orcid.org/0000-0002-9463-8181)
- Hayama Tsutsumi (ORCID: https://orcid.org/0000-0003-4735-9670)
- Noriko Sato (ORCID: https://orcid.org/0000-0002-9305-7131)
- Toshiaki Sunazuka (ORCID: https://orcid.org/0000-0002-8001-081X)
Institutions
- University of Tsukuba (JP)
- University of the Ryukyus (JP)
- Kitasato Institute Hospital (JP)
- Kitasato University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c00824
- Citations
- 2
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 3.76