Inhibitory effects of sesquiterpene lactones from the Indonesian marine sponge Lamellodysidea cf. herbacea on bone morphogenetic protein-induced osteoblastic differentiation

Satoshi Ohte; Hiroyuki Yamazaki; Ohgi Takahashi; Henki Rotinsulu; Defny S Wewengkang; Deiske A Sumilat; Delfly B Abdjul; Wilmar Maarisit; Magie M Kapojos; Huiping Zhang; Fumiaki Hayashi; Michio Namikoshi; Takenobu Katagiri; Hiroshi Tomoda; Ryuji Uchida

doi:10.1016/j.bmcl.2021.127783

Inhibitory effects of sesquiterpene lactones from the Indonesian marine sponge Lamellodysidea cf. herbacea on bone morphogenetic protein-induced osteoblastic differentiation

Bioorg Med Chem Lett. 2021 Mar 1:35:127783. doi: 10.1016/j.bmcl.2021.127783. Epub 2021 Jan 8.

Authors

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: ohtes@pharm.kitasato-u.ac.jp.
² Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
³ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
⁴ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
⁵ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; North Sulawesi Research and Development Agency, 17 Agustus Street, Manado 95117, Indonesia.
⁶ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; Faculty of Mathematics and Natural Sciences, Christian University of Indonesia, Tomohon 95362, Indonesia.
⁷ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; Faculty of Nursing, University of Pembangunan Indonesia, Bahu, Manado 95115, Indonesia.
⁸ NMR Science and Development Division, RIKEN SPring-8 Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
⁹ Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan.
¹⁰ Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
¹¹ Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan. Electronic address: uchidar@tohoku-mpu.ac.jp.

PMID: 33422607
DOI: 10.1016/j.bmcl.2021.127783

Abstract

A new unique sesquiterpene lactone, bicyclolamellolactone A (1), was isolated together with two known monocyclofarnesol-type sesquiterpenes, lamellolactones A (2) and B (3), from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea). The planar structure of 1 was assigned based on its spectroscopic data (1D and 2D NMR, HRESIMS, UV, and IR spectra). The relative and absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism spectra in combination with NOESY correlations. Compounds 1-3 inhibited bone morphogenic protein (BMP)-induced alkaline phosphatase activity in mutant BMP receptor-carrying C2C12 cells with IC₅₀ values of 51, 4.6, and 20 μM, respectively.

Keywords: Bone morphogenic protein-induced alkaline phosphatase; Fibrodysplasia ossificans progressive; Marine sponge Lamellodysidea cf. herbacea; Sesquiterpene lactone; bicyclolamellolactone A.

Publication types

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

MeSH terms

Alkaline Phosphatase / antagonists & inhibitors
Alkaline Phosphatase / metabolism
Animals
Bone Morphogenetic Proteins / antagonists & inhibitors*
Bone Morphogenetic Proteins / metabolism
Cell Differentiation / drug effects
Cell Line
Dose-Response Relationship, Drug
Indonesia
Lactones / chemistry
Lactones / isolation & purification
Lactones / pharmacology*
Mice
Molecular Structure
Osteoblasts / drug effects*
Osteoblasts / metabolism
Porifera / chemistry*
Sesquiterpenes / chemistry
Sesquiterpenes / isolation & purification
Sesquiterpenes / pharmacology*
Structure-Activity Relationship

Substances

Bone Morphogenetic Proteins
Lactones
Sesquiterpenes
Alkaline Phosphatase