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Voluhemins, new inhibitors of sterol O-acyltransferase, produced by Volutella citrinella BF-0440

The Journal of Antibiotics volume 73, pages 748–755 (2020)Cite this article

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Abstract

New compounds, designated voluhemins A (1) and B (2), are isolated from the culture broth of the fungal strain Volutella citrinella BF-0440 along with structurally related known NK12838 (3). Spectroscopic data, including 1D and 2D NMR, elucidated their structures. Compounds 1–3 have a common indoline-diterpene core and two additional isoprenyl moieties. Compounds 1 and 3 contain a hemiaminal unit, while 2 is O-methylated 1. Their inhibitory activities toward sterol O-acyltransferase (SOAT) 1 and 2 isozymes in SOAT1- and SOAT2-expressing Chinese hamster ovary (CHO) cells show that 2 selectively inhibits the SOAT2 isozyme.

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Acknowledgements

This work is dedicated to the late Prof. Lawrence L. Rudel (Wake Forest University, Winston-Salem, NC, USA), who always helped and encouraged our work on SOAT2 inhibitors. We wish to thank Ms Noriko Sato and Dr Kenichiro Nagai (Graduate School of Pharmaceutical Sciences, Kitasato University) for the measurements of the NMR spectra and MS data, and Prof. L.L. Rudel for kindly providing SOAT1-CHO and SOAT2-CHO cells. This work was supported by JSPS KAKENHI [Grant numbers JP26253009 (HT) and JP18K06555 (TO)] and the Takeda Science Foundation (HT).

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  1. Taichi Ohshiro

    Present address: Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

Authors and Affiliations

  1. Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Taichi Ohshiro, Haruka Morita, Elyza Aiman Azizah Nur, Kanji Hosoda & Hiroshi Tomoda

  2. Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Taichi Ohshiro, Kanji Hosoda & Hiroshi Tomoda

  3. Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan

    Ryuji Uchida

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Ohshiro, T., Morita, H., Nur, E.A.A. et al. Voluhemins, new inhibitors of sterol O-acyltransferase, produced by Volutella citrinella BF-0440. J Antibiot 73, 748–755 (2020). https://doi.org/10.1038/s41429-020-0327-0

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