Design, Synthesis and Biological Evaluation of Caudatin Analogs as Potent Hepatitis B Virus Inhibitors

Wang, Lijun; Chen, Hao; Ma, Yun‐Bao; Huang, Xiaoyan; Geng, Chang‐An; Zhang, Xuemei; Chen, Ji‐Jun

doi:10.2174/1573406410666140902111326

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…Helioxanthin analogues as shown in Figure , presumed HBV viral transcription inhibitors, were discovered from a natural source. Many natural products have been reported to show inhibitory activities against HBV with however often weak ones. − As shown in Figure , a number of examples including 54 (robustaflavone) and 55 (caudatin) demonstrated in vitro activities against HBV DNA replication in HepG2.2.15 cells with IC 50 values from sub-μM to double-digit μM range. Moreover, 56 (alisol A) and 57 (vanitaracin A) were shown to inhibit HBsAg with IC 50 values of 39 and 10.5 μM in HepG2.2.15 and HepG2-hNTCP-C4 cells, respectively (Figure ).…”

Section: Therapeutic Approaches For Hepatitis B Virus Treatmentmentioning

confidence: 99%

Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection

et al. 2017

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For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products. Compounds that exert their antiviral activities mainly through host factors and immunomodulation, such as host targeting agents (HTAs), programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, and Toll-like receptor (TLR) agonists, are also discussed. In this Perspective, we hope to provide an overview, albeit by no means being comprehensive, for the recent development of novel therapeutic agents for the treatment of chronic HBV infection, which not only are able to sustainably suppress viral DNA but also aim to achieve functional cure warranted by HBsAg loss and ultimately lead to virus eradication and cure of hepatitis B.

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Section: Therapeutic Approaches For Hepatitis B Virus Treatmentmentioning

confidence: 99%

Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection

et al. 2017

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“…HDACs are a class of epigenetic enzymes that are closely related to the occurrence and development of tumor, and are an important target family for the treatment of cancer, inflammation, and nervous system diseases (Duan et al., 2023; He et al., 2022), and play a key regulatory role in cell growth, differentiation, and apoptosis. In addition, HDACs also are overexpressed in most tumor cells, which are involved in tumor genesis and invasion (Cress & Seto, 2000).…”

Section: Introductionmentioning

confidence: 99%

Discovering novel derivatives of STAT3 and HDAC inhibitors with anti‐tumor activity

Yang,

Pu,

Huang

et al. 2024

Chem Biol Drug Des

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In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual‐target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS‐275. Among them, compound 24 (IC50 = 8.22 ± 0.27 μM) showed better anti‐tumor activity than the clinical Class I HDAC inhibitor MS‐275 (IC50 = 14.65 ± 0.24 μM) in MCF‐7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3–HDAC pathway inhibitor achieved with a single molecule.

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“…Methods to stop and eliminate HBV DNA and cccDNA from HBV patients are still a great challenge for researchers. In searching for more effective anti-HBV agents, many significant anti-HBV non-nucleoside analogs from synthesized compounds [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and natural products [ 24 , 25 , 26 ] have been found. Some were designed according to their interactions with receptor by simulating screen [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation

et al. 2018

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A series of oxime ethers with C6-C4 fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel–Crafts reaction, esterification (or amidation), and oximation from p-substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound 5c-1 showed the most potent activity on inhibiting HBsAg secretion (IC50 = 39.93 μM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.

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Design, Synthesis and Biological Evaluation of Caudatin Analogs as Potent Hepatitis B Virus Inhibitors

Cited by 6 publications

References 24 publications

Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection

Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection

Discovering novel derivatives of STAT3 and HDAC inhibitors with anti‐tumor activity

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation

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