MEDICINAL CHEMISTRY RESEARCH
·
2023
·Vol. 32
·期 5
·899-909
·
IF 2.6
Ye Zhen,Zhao Tong-Shi-Yao,Li Shan-Bin,Zhou Xian-Li,Luo Qin,Qin Jiang-Ke,Liang Cheng-Qin,Wang Ping,Ge Guang-Bo
Previous in vivo and in vitro studies revealed that esculetin (Fig. 1 ) has anti-hepatitis B virus (anti-HBV) activity as well as a protective effect on liver damage caused by duck hepatitis B virus. We designed and synthesized a series of esculetin derivatives, introduced side chains containing various amino groups into site 7 of the parent structure, and synthesized C-4 and C-8 substituted derivatives with the goal of investigating their anti-HBV activities. In vitro anti-HBV activity was performed against HepG2.2.15 cells by using Enzyme-Linked Immunosorbent Assay(ELISA) kit and cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay with lamivudine as the positive control. The results demonstrated that several compounds showed moderate anti-HBV activity, while the introduction of morpholine groups could significantly inhibit the expression of hepatitis B e antigen (HBeAg) and the introduction of the 2-methylimidazole group could significantly inhibit the expression of Hepatitis B surface antigen (HBsAg). Among all tested compounds, compound 4a demonstrated the best anti-HBeAg activity (IC 50 = 15.8 ± 4.2 μM), while compound 6d demonstrated the best anti-HBsAg activity (IC 50 = 21.4 ± 2.8 μM). Compounds 6b and 6c showed moderate anti-HBV activity and HBsAg inhibition. Compounds 4b showed moderate anti-HBV activity and an inhibitory effect on HBeAg. In addition, compounds 4a , 4c , 4d , 6b , 6c and 6d showed improved metabolic stability. This study provides useful guidance for the discovery of anti-HBV drugs, which merits further investigation. Graphical Abstract
研究领域:
药理学
·
病毒学
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DOI
PubMed
高影响因子
Nutrients
·
2024
·Vol. 16
·期 5
·600
·
IF 4.8
Juan Yang,He Gao,Tiantian Zhang,Yong Fan,Yuwei Wu,Xinyu Zhao,Ying Li,Lei Wu,Hui Zhao,Lingshuang Yang,Haojie Zhong,Longyan Li,Xinqiang Xie,Qingping Wu
Hepatocellular carcinoma (HCC), being ranked as the top fifth most prevalent cancer globally, poses a significant health challenge, with a considerable mortality rate. Hepatitis B virus (HBV) infection stands as the primary factor contributing to HCC, presenting substantial challenges in its treatment. This study aimed to identify lactic acid bacteria (LAB) with anti-HBV properties and evaluate their impact on the intestinal flora in HBV-associated HCC. Initially, two LAB strains,Levilactobacillus brevisSR52-2 (L. brevisSR52-2) andLeviLactobacillus delbrueckiisubsp.bulgaicusQ80 (L. delbrueckiiQ80), exhibiting anti-HBV effects, were screened in vitro from a pool of 498 LAB strains through cell experiments, with extracellular expression levels of 0.58 ± 0.05 and 0.65 ± 0.03, respectively. These strains exhibited the capability of inhibiting the expression of HBeAg and HBsAg. Subsequent in vitro fermentation, conducted under simulated anaerobic conditions mimicking the colon environment, revealed a decrease in pH levels in both the health control (HC) and HCC groups influenced by LAB, with a more pronounced effect observed in the HC group. Additionally, the density of total short-chain fatty acids (SCFAs) significantly increased (p< 0.05) in the HCC group. Analysis of 16S rRNA highlighted differences in the gut microbiota (GM) community structure in cultures treated withL. brevisSR52-2 andL. delbrueckiiQ80. Fecal microflora in normal samples exhibited greater diversity compared to HBV-HCC samples. The HCC group treated with LAB showed a significant increase in the abundance of the phyla Firmicutes, Bacteroidetes and Actinobacteria, while Proteobacteria significantly decreased compared to the untreated HCC group after 48 h. In conclusion, the findings indicate that LAB, specificallyL. brevisSR52-2 andL. delbrueckiiQ80, possessing antiviral properties, contribute to an improvement in gastrointestinal health.
研究领域:
微生物学
·
医学研究
·
癌症生物学
·
病毒学
·
胃肠病学
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DOI
PubMed
高影响因子
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