文献类型：期刊文献

英文题名：18(3-glycyrrhetinic acid-amantadine hybrid: Synthesis and anti-EMCV activity via NF-κB modulation

作者：Xue, Weijiao[1,2];Zhang, Tengyu[1];Wen, Yanqiao[3,4];Zhang, Yan[1,2];Hou, Jixia[1];Zhao, Jieying[1];Feng, Ruofei[3,4];Tan, Chunxia[1,2]

第一作者：Xue, Weijiao

通信作者：Tan, CX[1];Feng, RF[2]

机构：[1]Gansu Univ Chinese Med, Lanzhou, Peoples R China;[2]Res Ctr Tradit Chinese Med, Lanzhou, Peoples R China;[3]Northwest Minzu Univ, Biomed Res Ctr, Key Lab Biotechnol & Bioengn State Ethn Affairs Co, Lanzhou, Peoples R China;[4]Northwest Minzu Univ, Sch Life Sci & Engn, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou, Peoples R China;[2]corresponding author), Northwest Minzu Univ, Biomed Res Ctr, Key Lab Biotechnol & Bioengn State Ethn Affairs Co, Lanzhou, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：131

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001593212600003)】；

基金：This study was supported by the Research Center for Traditional Chinese Medicine, Gansu Province (zyzx-2023-22). Natural Science Foundation of Gansu Province (CN) (22JR11RA119), and Biomedical Research Center of Northwest Minzu University (BRC-KF202303).

语种：英文

外文关键词：18(3-Glycyrrhetinic acid; Synthesis; Characterization; Antiviral activity; EMCV

摘要：Encephalomyocarditis virus (EMCV) is an important pathogen; however, current prevention and treatment methods and drugs are limited. 18(3-Glycyrrhetinic acid (GA) is widely used in traditional Chinese medicine as a key active ingredient in Glycyrrhiza glabra and has anti-inflammatory, antiviral, antioxidant, and hepatoprotective pharmacological effects. However, the bioavailability of GA is significantly reduced by its low water solubility and high toxicity. Amantadine (AM) is a versatile antiviral drug. We reduced the toxicity and increased the bioavailability of GA by introducing AM into the GA backbone, and further explored its antiviral mechanism. The chemical structures of the new 18(3-glycyrrhetinic acid derivative grafted with amantadine (GAAM) were confirmed by IR, 1HNMR and ESI-MS. The cytotoxicity of GA-AM in BHK-21 and HEK-293 cells was determined using the CCK-8 assay. The antiviral effect and mechanism of action of the EMCV virus of GA-AM were detected in vitro and in vivo using TCID50, RT-qPCR, Western blotting, IFA, and ELISA. Compared to GA, GA-AM exhibited lower cytotoxicity in BHK-21 and HEK-293T cells and demonstrated more significant antiviral effects against EMCV. GA-AM can also protect EMCV-infected cells and reduce the amount of the VP1 capsid protein in cells. Mechanistic investigations revealed that GA-AM might exert antiviral effects by regulating the NF-kappa B signaling pathway and modulating downstream cytokines, including TNF-alpha and IL-6. Furthermore, GA-AM alleviated these signs in EMCV-infected mice. The novel drug GA-AM has lower cytotoxicity and more significant antiviral effects. It may therefore serve as a new, low-toxicity antiviral agent.