Spiroconyone A, a new phytosterol with a spiro [5,6] ring system from Conyza japonica.
A549 Cells
Animals
Conyza
/ chemistry
Crystallography, X-Ray
Drug Screening Assays, Antitumor
Humans
Inhibitory Concentration 50
MCF-7 Cells
Mass Spectrometry
/ methods
Mice
Molecular Structure
Phosphoric Diester Hydrolases
/ drug effects
Phytosterols
/ chemistry
Proton Magnetic Resonance Spectroscopy
Spectrophotometry, Ultraviolet
Journal
Organic & biomolecular chemistry
ISSN: 1477-0539
Titre abrégé: Org Biomol Chem
Pays: England
ID NLM: 101154995
Informations de publication
Date de publication:
15 07 2020
15 07 2020
Historique:
pubmed:
8
5
2020
medline:
12
8
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Spiroconyone A (1), the first rearranged phytosterol featuring an unusual spiro [5,6] ring system, and nine known compounds (2-10) were isolated from the aerial parts of Conyza japonica. The structure of 1 was elucidated through spectroscopic methods, and its absolute configuration was determined by single-crystal X-ray diffraction analysis. Enzyme-based assay revealed that spiroconyone A showed weak TDP1 inhibition and compounds 7 and 10 showed TDP1 inhibition with IC50 values of 36 μM and 16 μM, respectively. MTT assay indicated that 7 and 10 showed a strong synergistic effect with the clinical TOP1 inhibitor topotecan in MCF-7 cells. Compound 5 displayed the most potent cytotoxicity against MCF-7 cells with a GI50 value of 3.3 μM. Furthermore, a hypothetical biosynthetic pathway for 1 was proposed. This work provides valuable information that the secondary metabolites from Conyza japonica could be developed as anticancer agents.
Substances chimiques
Phytosterols
0
Phosphoric Diester Hydrolases
EC 3.1.4.-
TDP1 protein, human
EC 3.1.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM