Design and synthesis of novel saponin-triazole derivatives in the regulation of adipogenesis.
10.1016/S1875-5364(25)60830-2
- Author:
Yongsheng FANG
1
;
Zhiyun ZHU
2
;
Chun XIE
2
;
Dazhen XIA
2
;
Huimin ZHAO
2
;
Zihui WANG
2
;
Qian LU
2
;
Caimei ZHANG
2
;
Wenyong XIONG
3
;
Xiaodong YANG
4
Author Information
1. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy; Yunnan University, Kunming 650500, China. Electronic address: ysfang@ucas.ac.cn.
2. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy; Yunnan University, Kunming 650500, China.
3. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy; Yunnan University, Kunming 650500, China. Electronic address: xwy@ynu.edu.cn.
4. Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy; Yunnan University, Kunming 650500, China. Electronic address: xdyang@ynu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Adipocyte differentiation and maturation;
Lipid metabolism;
Panax notoginseng;
Saponin-triazole derivatives;
Structure-activity relationships
- MeSH:
Adipogenesis/drug effects*;
Triazoles/chemical synthesis*;
Ginsenosides/chemical synthesis*;
Saponins/chemical synthesis*;
Animals;
Mice;
Structure-Activity Relationship;
PPAR gamma/genetics*;
3T3-L1 Cells;
Adipocytes/metabolism*;
Panax notoginseng/chemistry*;
Drug Design;
Molecular Structure;
Humans;
Cell Differentiation/drug effects*;
Fatty Acid-Binding Proteins/genetics*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(8):920-931
- CountryChina
- Language:English
-
Abstract:
Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
