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

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.

journal_name

Fitoterapia

journal_title

Fitoterapia

authors

Shimizu E,Koshino H,Noro A,Maruyama M,Shimoda N,Uesugi S,Ohnishi M,Kimura KI

doi

10.1016/j.fitote.2019.02.027

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

290-296

eissn

0367-326X

issn

1873-6971

pii

S0367-326X(18)32422-5

journal_volume

134

pub_type

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