Discovery of a novel anti-osteoporotic agent from marine fungus-derived structurally diverse sirenins.
Eur J Med Chem
; 265: 116068, 2024 Feb 05.
Article
in En
| MEDLINE
| ID: mdl-38141284
ABSTRACT
Thirteen new sirenin derivatives named eupenicisirenins C-O (1-13), along with a biosynthetically related known one (14), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data, quantum chemical calculations, and X-ray diffraction. Among them, eupenicisirenin C (1) exhibited the strongest NF-κB inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoporosis
/
Penicillium
Limits:
Animals
Language:
En
Journal:
Eur J Med Chem
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
France