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Axl and immune checkpoints inhibitors from fruiting bodies of Pleurocybella porrigens

The Journal of Antibiotics volume 73, pages 733–736 (2020)Cite this article

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Abstract

A novel compound (1) and three known ones (2−4) were isolated from the fruiting bodies of Pleurocybella porrigens. The structure of the novel compound was determined by 1D and 2D NMR and HRESIMS data. The biological activity of 1−3 was evaluated using the A549 lung cancer cell line. The results showed the inhibitory activity of compounds 1−3 on the expression of Axl and immune checkpoint molecules.

In 2004, there was a poisoning outbreak affecting 55 Japanese people after eating the wild mushroom Pleurocybella porrigens (Sugihiratake in Japanese). Among them, seventeen people died due to acute encephalopathy. This outbreak has led to several investigations to clarify the mechanism of mushroom poisoning. In recent years, our group has reported the isolation and characterization of a novel lectin and unusual amino acids from P. porrigens [1, 2]. Our subsequent investigation led to the discovery of pleurocybellaaziridine, a structurally-unique and unstable amino acid as the candidate of toxic principle [3]. Studies by other groups also suggested that the poisoning outbreak might have been caused by vitamin D analogue, cyanide and thiocyanate [4, 5]. Despite the highly toxic nature of P. porrigens, only a few studies on metabolites with physiological activity have been so far reported. Apart from elucidating the molecular mechanism of the disease caused by the fungus, we are also interested in search for bioactive secondary metabolites produced by P. porrigens, because the fungus produces structurally unique compounds such as pleurocybellaaziridine. Recently, we are focusing on search for Axl and immune checkpoints (PD-L1/PD-L2) inhibitors from natural sources, especially mushroom-forming fungi.

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Fig. 1
Fig. 2

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Acknowledgements

This research was funded by a Grant-in Aid for Scientific Research on Innovative Areas “Frontier Research on Chemical Communications” from MEXT (No 17H06402) and Specific Research Grant from Takeda Science Foundation.

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Authors and Affiliations

  1. Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan

    Arif Yanuar Ridwan, Jae-Hoon Choi, Hirofumi Hirai & Hirokazu Kawagishi

  2. Research Institute of Green Science and Technology, Shizuoka University, Shizuoka, Japan

    Jing Wu, Jae-Hoon Choi, Hirofumi Hirai & Hirokazu Kawagishi

  3. Department of Forest and Environmental Science, Miyazaki University, Miyazaki, Japan

    Etsuko Harada

  4. Department of Immunology, Graduate School of Medicine, Mie University, Mie, Japan

    Corina N. D´Alessandro-Gabazza, Masaaki Toda, Taro Yasuma & Esteban C. Gabazza

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  1. Arif Yanuar Ridwan
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Correspondence to Hirokazu Kawagishi.

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Ridwan, A.Y., Wu, J., Harada, E. et al. Axl and immune checkpoints inhibitors from fruiting bodies of Pleurocybella porrigens. J Antibiot 73, 733–736 (2020). https://doi.org/10.1038/s41429-020-0323-4

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