Abstract
Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus Tolypocladium album RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC50 value of 0.79 µg/ml, while > 30 µg/ml of IC50 value in a normal condition, and inhibited a mitochondrial respiration.
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Acknowledgements
We would like to thank to Dr R. Uson-Lopez, Dr M. Uchida, Ms E. Sanada in RIKEN for supporting the activity tests, and Ms A. Hiraki in RIKEN for the collection of a soil. This work was supported in part by the JSPS KAKENHI (JP17K07784, JP16K01941, JP17H06412, and JP18H03945) and AMED under Grant Number JP19cm0106112.
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Nogawa, T., Kawatani, M., Okano, A. et al. Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007. J Antibiot 72, 996–1000 (2019). https://doi.org/10.1038/s41429-019-0229-1
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DOI: https://doi.org/10.1038/s41429-019-0229-1
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