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


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 13 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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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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Correspondence to Taichi Ohshiro or Hiroshi Tomoda.

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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).

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