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

Taichi Ohshiro; Haruka Morita; Elyza Aiman Azizah Nur; Kanji Hosoda; Ryuji Uchida; Hiroshi Tomoda

doi:10.1038/s41429-020-0327-0

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

J Antibiot (Tokyo). 2020 Nov;73(11):748-755. doi: 10.1038/s41429-020-0327-0. Epub 2020 May 29.

Authors

Taichi Ohshiro^{1

2

3}, Haruka Morita⁴, Elyza Aiman Azizah Nur⁴, Kanji Hosoda^{4

5}, Ryuji Uchida⁶, Hiroshi Tomoda^{7

8}

Affiliations

¹ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tohshiro@med.nagoya-u.ac.jp.
² Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tohshiro@med.nagoya-u.ac.jp.
³ Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. tohshiro@med.nagoya-u.ac.jp.
⁴ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
⁵ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
⁶ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi, 981-8558, Japan.
⁷ Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tomodah@pharm.kitasato-u.ac.jp.
⁸ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. tomodah@pharm.kitasato-u.ac.jp.

PMID: 32467602
DOI: 10.1038/s41429-020-0327-0

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CHO Cells / drug effects
CHO Cells / enzymology
Cricetulus
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification*
Enzyme Inhibitors / pharmacology
Hypocreales / chemistry*
Hypocreales / metabolism
Magnetic Resonance Spectroscopy
Molecular Structure
Sterol O-Acyltransferase / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Sterol O-Acyltransferase

Supplementary concepts

Volutella citrinella