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2 results on '"Katagiri T"'

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

Author

Ohte S, Yamazaki H, Takahashi O, Rotinsulu H, Wewengkang DS, Sumilat DA, Abdjul DB, Maarisit W, Kapojos MM, Zhang H, Hayashi F, Namikoshi M, Katagiri T, Tomoda H, and Uchida R

Subjects
Alkaline Phosphatase antagonists & inhibitors, Alkaline Phosphatase metabolism, Animals, Bone Morphogenetic Proteins metabolism, Cell Differentiation drug effects, Cell Line, Dose-Response Relationship, Drug, Indonesia, Lactones chemistry, Lactones isolation & purification, Mice, Molecular Structure, Osteoblasts metabolism, Sesquiterpenes chemistry, Sesquiterpenes isolation & purification, Structure-Activity Relationship, Bone Morphogenetic Proteins antagonists & inhibitors, Lactones pharmacology, Osteoblasts drug effects, Porifera chemistry, Sesquiterpenes pharmacology
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 IC 50 values of 51, 4.6, and 20 μM, respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Published
2021
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2. Screening for Small Molecule Inhibitors of BMP-Induced Osteoblastic Differentiation from Indonesian Marine Invertebrates.

Author

Yamazaki H, Ohte S, Rotinsulu H, Wewengkang DS, Sumilat DA, Abdjul DB, Maarisit W, Kapojos MM, Namikoshi M, Katagiri T, Tomoda H, and Uchida R

Subjects
Alkaline Phosphatase metabolism, Animals, Bone Morphogenetic Protein 4 toxicity, Cell Line, Enzyme Inhibitors isolation & purification, Indonesia, Mice, Molecular Structure, Myoblasts, Skeletal metabolism, Myoblasts, Skeletal pathology, Myositis Ossificans metabolism, Myositis Ossificans pathology, Osteoblasts metabolism, Osteoblasts pathology, Sterols isolation & purification, Structure-Activity Relationship, Thiazoles isolation & purification, Alkaline Phosphatase antagonists & inhibitors, Cell Differentiation drug effects, Dysidea metabolism, Enzyme Inhibitors pharmacology, Myoblasts, Skeletal drug effects, Myositis Ossificans drug therapy, Osteoblasts drug effects, Osteogenesis drug effects, Sterols pharmacology, Thiazoles pharmacology
Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder with heterotopic ossification (HO) in soft tissues. The abnormal activation of bone morphogenetic protein (BMP) signaling by a mutant activin receptor-like kinase-2 (ALK2) leads to the development of HO in FOP patients, and, thus, BMP signaling inhibitors are promising therapeutic applications for FOP. In the present study, we screened extracts of 188 Indonesian marine invertebrates for small molecular inhibitors of BMP-induced alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation in a C2C12 cell line stably expressing ALK2(R206H) (C2C12(R206H) cells), and identified five marine sponges with potent ALP inhibitory activities. The activity-guided purification of an EtOH extract of marine sponge Dysidea sp. (No. 256) resulted in the isolation of dysidenin ( 1 ), herbasterol ( 2 ), and stellettasterol ( 3 ) as active components. Compounds 1 - 3 inhibited ALP activity in C2C12(R206H) cells with IC 50 values of 2.3, 4.3, and 4.2 µM, respectively, without any cytotoxicity, even at 18.4-21.4 µM. The direct effects of BMP signaling examined using the Id1WT4F-luciferase reporter assay showed that compounds 1 - 3 did not decrease the reporter activity, suggesting that they inhibit the downstream of the Smad transcriptional step in BMP signaling.

Published
2020
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