Curvularin derivatives from hydrothermal vent sediment fungus Penicillium sp. HL-50 guided by molecular networking and their anti-inflammatory activity.
10.1016/S1875-5364(25)60803-X
- Author:
Chunxue YU
1
;
Zixuan XIA
1
;
Zhipeng XU
1
;
Xiyang TANG
1
;
Wenjuan DING
2
;
Jihua WEI
3
;
Danmei TIAN
4
,
5
;
Bin WU
6
;
Jinshan TANG
5
,
7
Author Information
1. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China.
2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
3. Ocean College, Zhejiang University, Zhoushan Campus, Zhoushan 316021, China.
4. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China. Electronic address: danmeitianjnu@
5. com.
6. Ocean College, Zhejiang University, Zhoushan Campus, Zhoushan 316021, China. Electronic address: wubin@zju.edu.cn.
7. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China. Electronic address: gztangjinshan@
- Publication Type:Journal Article
- Keywords:
Anti-inflammatory activity;
Curvularin derivatives;
Molecular networking;
Penicillium sp. HL-50
- MeSH:
Penicillium/chemistry*;
Mice;
Animals;
Anti-Inflammatory Agents/isolation & purification*;
RAW 264.7 Cells;
Nitric Oxide/metabolism*;
Hydrothermal Vents/microbiology*;
Macrophages/immunology*;
Molecular Structure;
Nitric Oxide Synthase Type II/immunology*;
Cyclooxygenase 2/immunology*;
Geologic Sediments/microbiology*;
NF-kappa B/immunology*;
NLR Family, Pyrin Domain-Containing 3 Protein/immunology*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(1):119-128
- CountryChina
- Language:English
-
Abstract:
Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, 13C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC50 values ranging from 0.44 to 4.40 μmol·L-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
