Synthesis and in vitro antiviral effects against hepatitis C virus of oleanolic acid and ursolic acid derivatives
10.12206/j.issn.2097-2024.202502045
- VernacularTitle:齐墩果酸和熊果酸衍生物的化学合成及体外抗丙肝病毒作用的研究
- Author:
Shuwen XIAO
1
;
Heyang ZHOU
2
;
Yongsheng JIN
3
;
Liming QIAO
3
;
Wei ZHENG
4
Author Information
1. Department of Pharmacy, The 80th Group Military Hospital of PLA, Weifang 261000, China.
2. Outpatient Department of Shenzhen Base of PLA Hong Kong Garrison, Shenzhen 518017, China.
3. School of Pharmacy, Naval Medical University, Shanghai 200433, China.
4. Department of Pharmacy, The 72nd Group Military Hospital of PLA, Huzhou 313000, China.
- Publication Type:Originalarticles
- Keywords:
pentacyclic triterpenoid acid;
derivatives;
antiviral effect against hepatitis C virus;
NS5B
- From:
Journal of Pharmaceutical Practice and Service
2025;43(10):503-508
- CountryChina
- Language:Chinese
-
Abstract:
Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.
