Diketopiperazines with anti-skin inflammation from marine-derived endophytic fungus Aspergillus sp. and configurational reassignment of aspertryptanthrins.
10.1016/S1875-5364(25)60933-2
- Author:
Jin YANG
1
;
Xianmei XIONG
2
;
Lizhi GONG
2
;
Fengyu GAN
2
;
Hanling SHI
2
;
Bin ZHU
2
;
Haizhen WU
2
;
Xiujuan XIN
2
;
Lingyi KONG
3
;
Faliang AN
4
Author Information
1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address: 592810782@qq.com.
2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
3. Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
4. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Marine Biomedical Science and Technology Innovation Platform of Lin-gang Special Area, Shanghai 201306, China. Electronic address: flan2016@ecust.edu.cn.
- Publication Type:Journal Article
- Keywords:
Anti-skin inflammation;
Aspergillus sp.;
Configurational reassignment;
Diketopiperazines
- MeSH:
Humans;
Aspergillus/chemistry*;
Diketopiperazines/isolation & purification*;
Anti-Inflammatory Agents/isolation & purification*;
Interleukin-1beta/genetics*;
Toll-Like Receptor 2/immunology*;
Propionibacterium acnes/drug effects*;
NF-kappa B/genetics*;
Molecular Structure;
Myeloid Differentiation Factor 88/immunology*;
Monocytes/immunology*;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*;
Cell Line
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(8):980-989
- CountryChina
- Language:English
-
Abstract:
Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
