TY - JOUR
T1 - Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007
AU - Nogawa, Toshihiko
AU - Kawatani, Makoto
AU - Okano, Akiko
AU - Futamura, Yushi
AU - Aono, Harumi
AU - Shimizu, Takeshi
AU - Kato, Naoki
AU - Kikuchi, Haruhisa
AU - Osada, Hiroyuki
N1 - Funding Information:
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.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41429-019-0229-1
DO - 10.1038/s41429-019-0229-1
M3 - Article
C2 - 31481762
AN - SCOPUS:85072211153
SN - 0021-8820
VL - 72
SP - 996
EP - 1000
JO - Journal of Antibiotics
JF - Journal of Antibiotics
IS - 12
ER -