Amakusamine from a Psammocinia sp. Sponge: Isolation, Synthesis, and SAR Study on the Inhibition of RANKL-Induced Formation of Multinuclear Osteoclasts

  • J Nat Prod. 2021 Oct 22;84(10):2738-2743. doi: 10.1021/acs.jnatprod.1c00758.
Yuka Maeyama  1 ,  Yuta Nakashima  2 ,  Hikaru Kato  1 ,  Yuki Hitora  1 ,  Kazuhiko Maki  1 ,  Natsumi Inada  1 ,  Shunya Murakami  1 ,  Tomoaki Inazumi  3 ,  Yuji Ise  4 ,  Yukihiko Sugimoto  3 ,  Hayato Ishikawa  5 ,  Sachiko Tsukamoto  1
Affiliations
  • 1. Department of Natural Medicines, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
  • 2. Graduate School of Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.
  • 3. Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
  • 4. Sesoko Station, University of the Ryukyus, 3422 Sesoko, Motobu, Okinawa 905-0227, Japan.
  • 5. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
PMID: 34612636 DOI: 10.1021/acs.jnatprod.1c00758
Abstract

A simple methylenedioxy dibromoindole alkaloid, amakusamine (1), was isolated from a marine Sponge of the genus Psammocinia, and its structure was determined from spectroscopic data, time-dependent density-functional theory calculations, and synthesis. Compound 1 inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinuclear osteoclasts with an IC50 value of 10.5 μM in RAW264 cells. The structure-activity relationship of 1 was also investigated with synthetic derivatives.

Products