Abstract
A new piperazine derivative designated helvamide was isolated as a pair of rotamers (1 and 2) from the culture broth of the fungus Aspergillus nidulans BF-0142 along with a known helvafuranone (3). The structures of 1 and 2 were elucidated based on spectroscopic analyses by the interpretation of one-dimensional and two-dimensional nuclear magnetic resonance data, ROESY (rotational Overhauser effect spectroscopy) correlations, and a chemical method. Helvamide existed as a rotameric mixture (1 and 2) in dimethyl sulfoxide. Helvamide inhibited sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT2) in enzyme-based and cell-based assays using SOAT1-expressing and SOAT2-expressing Chinese hamster ovary (CHO) cells.
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Acknowledgements
We thank Ms. Noriko Sato (School of Pharmaceutical Sciences, Kitasato University) for the measurements of NMR spectra and Prof. LL Rudel (Wake Forest University, Winston-Salem, NC, USA) for kindly providing SOAT1-CHO and SOAT2-CHO cells. This work was supported by JSPS KAKENHI Grant Number 15K07417 (to TF), JSPS KAKENHI Grant number JP26253009 (to HT), and the Takeda Science Foundation (to HT).
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Fukuda, T., Furukawa, T., Kobayashi, K. et al. Helvamide, a new inhibitor of sterol O-acyltransferase produced by the fungus Aspergillus nidulans BF-0142. J Antibiot 72, 8–14 (2019). https://doi.org/10.1038/s41429-018-0101-8
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DOI: https://doi.org/10.1038/s41429-018-0101-8
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