Format

Send to

Choose Destination
Fitoterapia. 2019 Apr;134:290-296. doi: 10.1016/j.fitote.2019.02.027. Epub 2019 Mar 2.

Isolation of a spirolactone norditerpenoid as a yeast Ca2+ signal transduction inhibitor from Kuji amber and evaluation of its effects on PPM1A activity.

Author information

1
Chemical Biology Laboratory, Iwate University, Morioka, Iwate 020-8550, Japan.
2
RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
3
Department of Biological Chemistry, Chubu University, Kasugai, Aichi 487-8501, Japan.
4
Chemical Biology Laboratory, Iwate University, Morioka, Iwate 020-8550, Japan. Electronic address: kimurak@iwate-u.ac.jp.

Abstract

A different type of biologically active compound from Kuji amber (Late Cretaceous, Japan) before the K-Pg boundary [65 million years ago (Ma)] was isolated based on the growth-restoring activity of a mutant yeast involving Ca2+ signal transduction. It was identified as a spirolactone norditerpenoid, (4R*, 5S*, 8R*, 9R*, 10S*)-14,15,16,19-tetranor-labdan-13,9-olide (1) from spectral analyses with high-resolution electron ionization mass spectrometry (HREIMS), 1D and 2D nuclear magnetic resonance (NMR). Although the planar structure of 1 is known as an artificial derivative from marrubiin, it was isolated as a natural product from Kuji amber and its structure was elucidated for the first time. It had a growth-restoring activity against the mutant yeast through the direct or indirect inhibition of calcineurin activity [protein phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A) activation]. Furthermore, the compound had potent inhibitory effect against the degranulation of rat basophilic leukemia 2H3 (RBL-2H3) cells.

KEYWORDS:

(4R*, 5S*, 8R*, 9R*, 10S*)-14,15,16,19-tetranor-labdan-13,9-olide; Kuji amber; PPM1A; RBL-2H3 cells; Saccharomyces cerevisiae; calcineurin

PMID:
30831200
DOI:
10.1016/j.fitote.2019.02.027
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center