Synthesis, pharmacological evaluation, and mechanistic study of adefovir mixed phosphonate derivatives bearing cholic acid and l-amino acid moieties for the treatment of HBV

Li, Tao; Li, Jing; Yang, Yang; Han, Yilin; Wu, Dirong; Xiao, Tao; Wang, Yang; Liu, Ting; Zhao, Yong‐Long; Li, Yongjun; Dai, Zeqin; Fu, Xiao‐Zhong

doi:10.1016/j.bmc.2019.07.012

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…Deoxycholic acid is a natural secondary hydrophilic cholic acid, which can prevent the formation of gallstones ( Song et al, 2020 ). Cholic acid-nucleoside analog conjugates can enhance the uptake of antiviral drugs by hepatocytes and increase the bioavailability of oral drugs ( Li et al, 2019 ). 3′,4′,7-Trihydroxyflavone has protective effects against acute liver injury in mice via alleviating inflammatory response, oxidative, and nitrosative stress burden, whose mechanism is about activating the Nrf2 and suppressing the TLR4/NF-κB signaling pathways ( Islam et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification

et al. 2023

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The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.

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Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification

et al. 2023

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“…The disadvantages of nucleoside analogs prompted us and other researchers to invent and find new structural non-nucleoside analog compounds [ 11 , 12 , 13 , 14 , 15 , 16 ]. Many anti-HBV bioactive non-nucleoside analog compounds have been designed and developed on the basis of their interactions with receptor using molecular docking [ 17 , 18 , 19 , 20 , 21 ]. When HBV receptor binding domain PreS1 and PreS2 protein (including L protein, M protein and S protein) interact with small molecules, the virus will not allow entry to hepatocyte.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

et al. 2020

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Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 μM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 μM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 μM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.

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Synthesis, pharmacological evaluation, and mechanistic study of adefovir mixed phosphonate derivatives bearing cholic acid and l-amino acid moieties for the treatment of HBV

Cited by 2 publications

References 28 publications

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification

Exploring the mechanism of JiGuCao capsule formula on treating hepatitis B virus infection via network pharmacology analysis and in vivo/vitro experiment verification

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

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