A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived Aspergillus sp. BFM-0085

Satoshi Ohte; Takehiro Shiokawa; Nobuhiro Koyama; Takenobu Katagiri; Chiaki Imada; Hiroshi Tomoda

doi:10.1038/s41429-020-0316-3

A new diketopiperazine-like inhibitor of bone morphogenetic protein-induced osteoblastic differentiation produced by marine-derived Aspergillus sp. BFM-0085

J Antibiot (Tokyo). 2020 Aug;73(8):554-558. doi: 10.1038/s41429-020-0316-3. Epub 2020 May 21.

Authors

Satoshi Ohte^{1

2

3}, Takehiro Shiokawa², Nobuhiro Koyama^{1

2

3}, Takenobu Katagiri⁴, Chiaki Imada⁵, Hiroshi Tomoda^{6

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.
² Department of Microbial Chemistry, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
³ Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
⁴ Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1241, Japan.
⁵ Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7, Konan, Minato-ku, Tokyo, 108-8477, Japan.
⁶ 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.
⁷ Department of Microbial Chemistry, School of Pharmacy, 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: 32439987
DOI: 10.1038/s41429-020-0316-3

Abstract

A new diketopiperazine-like compound, designated protuboxepin K (1), was isolated together with the known structurally related protuboxepin A (2) from culture broth of the marine-derived fungal strain Aspergillus sp. BFM-0085 isolated from a sediment sample of Tokyo Bay. The structure of protuboxepin K was elucidated by spectroscopic data, including 1D and 2D NMR. Compounds 1 and 2 inhibited bone morphogenetic protein (BMP)-induced alkaline phosphatase activity with IC₅₀ values of 4.7 and 25.2 μM, respectively, in mutant BMP receptor-carrying C2C12(R206H) cells.

Publication types

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

MeSH terms

Animals
Aquatic Organisms / chemistry*
Aspergillus / chemistry*
Bone Morphogenetic Proteins / antagonists & inhibitors*
Cell Differentiation / drug effects*
Cell Line
Diketopiperazines / pharmacology*
Mice
Osteoblasts / drug effects*
Osteoblasts / metabolism

Substances

Bone Morphogenetic Proteins
Diketopiperazines