Azaphilone derivatives with RANKL-induced osteoclastogenesis inhibition from the mangrove endophytic fungus Diaporthe sp.
10.1016/S1875-5364(25)60974-5
- Author:
Miaoping LIN
1
;
Yanhui TAN
2
;
Humu LU
3
;
Yuyao FENG
3
;
Min LI
2
;
Chenghai GAO
3
;
Yonghong LIU
4
;
Xiaowei LUO
5
,
6
Author Information
1. Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China; The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
2. State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
3. Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
4. Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China. Electronic address: yonghongliu@scsio.ac.cn.
5. Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China. Electronic address: luoxiaowei1991@
6. com.
- Publication Type:Journal Article
- Keywords:
Anti-osteoclastogenesis;
Azaphilones;
Diaporthe sp.;
Marine fungus
- MeSH:
Animals;
Mice;
RANK Ligand/genetics*;
RAW 264.7 Cells;
Osteoclasts/metabolism*;
Benzopyrans/isolation & purification*;
Osteogenesis/drug effects*;
Macrophages/metabolism*;
Molecular Structure;
Pigments, Biological/isolation & purification*;
Ascomycota/chemistry*;
NF-kappa B/genetics*;
Cell Differentiation/drug effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(9):1143-1152
- CountryChina
- Language:English
-
Abstract:
This study identified six novel azaphilones, isochromophilones G-L (1-6), and three novel biosynthetically related congeners (7-9) from Diaporthe sp. SCSIO 41011. The structures and absolute configurations were elucidated through comprehensive spectroscopic analyses combined with experimental and calculated electronic circular dichroism (ECD) spectra. Significantly, three highly oxygenated azaphilones contain an acetyl group at the terminal chain (4) or linear conjugated polyenoid moieties (5 and 6), which occur infrequently in the azaphilone family. Additionally, several compounds demonstrated inhibition of lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) activation in RAW 264.7 macrophages at 20 μmol·L-1. The novel compound (1) effectively inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation without exhibiting cytotoxicity in bone marrow and RAW 264.7 macrophages, indicating its potential as a promising lead compound for osteolytic disease treatment. This research presents the first documented evidence of azaphilone derivatives as inhibitors of RANKL-induced osteoclastogenesis.
