Amycolatopsis sp. OK19-0009产生的具有线粒体功能抑制活性的抗疟异腈化合物A和B。

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-09-30 DOI:10.1021/acs.jnatprod.5c00824

Emi Arakawa, Yoshihiro Watanabe, Hayama Tsutsumi, Akari Ikeda, Tomoyasu Hirose, Noriko Sato, Takumi Chinen, Akira Také, Hiroki Kanto, Yuki Inahashi, Takahiro Ishii, Toshiaki Teruya, Toshiaki Sunazuka, Hideaki Hanaki, Takeo Usui, Rei Hokari, Aki Ishiyama, Yukihiro Asami, Masato Iwatsuki

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引用次数: 0

摘要

从冲绳稀有放线菌Amycolatopsis sp. OK19-0009菌株的培养液中，采用生物测定指导分离法对多药敏感出芽酵母进行线粒体功能抑制活性测定，分离出两种新型抗疟药ufisonitriles A(1)和B(2)。采用HR-ESI-MS、1D/2D核磁共振分析和改进的Mosher法对其结构进行了全面鉴定。在结构上，1和2具有具有异氰基的新骨架。体外抗疟试验表明，1和2对恶性疟原虫的IC50值在28.6 ~ 1.12 μM之间，表现出中等水平的抗疟活性。此外，1和2通过腹腔给药（30 mg/kg/天，连续4天）可使体内疟原虫减少约45%，未观察到毒性。我们还提供了基于基因组序列分析的合理的生物合成途径。

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Ufisonitriles A and B, Antimalarial Isonitriles with Mitochondrial Function Inhibitory Activity Produced by Amycolatopsis sp. OK19-0009.

Two novel antimalarials, named ufisonitriles A (1) and B (2), 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 Amycolatopsis 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, 1 and 2 possess a novel skeleton with an isocyano group. In vitro antimalarial evaluation against Plasmodium falciparum strains revealed that 1 and 2 exhibited moderate activity with IC₅₀ values ranging from 28.6 to 1.12 μM. Furthermore, 1 and 2 reduced the malaria parasites by approximately 45% in vivo 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.

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.