Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

Cui, Xinhua; Zhou, Min; Tan, Jie; Wei, Zhuocai; Wei, Wanxing; Luo, Peng; Lin, Cui-Wu

doi:10.3390/molecules24112063

Cited by 2 publications

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References 29 publications

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“…The levels of HBeAg and HBsAg in the supernatant of the cells were measured using ELISA assay following the manufacturer's protocol (Shanghai Kehua Bio-engineering Co., Ltd., Shanghai, China). The synthesized compounds were expressed as the concentration that achieved 50% inhibition (IC 50 ) to the secretion of HBeAg and HBsAg [29].…”

Section: Methods For Cell Toxicity and Hbsag And Hbeag Inhibition Assaysmentioning

confidence: 99%

“…Therefore DHCA, with reactive functional groups, was considered as a liver-target vehicle to deliver drugs to the liver in our present work. Based on the bioactivities of DHCA and oximes in our previous works [28][29][30], the introduction of the oxime group to DHCA should be suggested to possess liver-targeted and anti-HBV activities. So, a series of oxime derivatives of DHCA were designed, synthesized, and screened for anti-HBV activity in vitro in this work, and molecular docking studies were carried out to investigate the relationship of structure and bioactivity of these compounds using a molecular operating environment (MOE).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Methods For Cell Toxicity and Hbsag And Hbeag Inhibition Assaysmentioning

confidence: 99%

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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<p>Synthesis and Bioactivity of <em>N</em>-(4-Chlorophenyl)-4-Methoxy-3-(Methylamino) Benzamide as a Potential Anti-HBV Agent</p>

Cui

Sun

Zhong

et al. 2020

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Introduction Hepatitis B virus (HBV) is a global health concern that can cause acute and chronic liver diseases. Thus, there is an urgent need to research novel anti-HBV agents. Our previous reports show that N -phenylbenzamide derivatives exert broad-spectrum antiviral effects against HIV-1, HCV, and EV71 by increasing intracellular levels of APOBEC3G (A3G). As A3G is capable of inhibiting the replication of HBV, we screened the N -phenylbenzamide derivatives against HBV. Methods In this study, a new derivative, N -(4-chlorophenyl)-4-methoxy-3-(methylamino) benzamide (IMB-0523), was synthesized and its anti-HBV activity was evaluated in vitro and in vivo. The acute toxicity and pharmacokinetic profiles of IMB-0523 were also investigated. Results Our results show that IMB-0523 has higher anti-HBV activity in both wild-type HBV (IC 50 : 1.99 µM) and drug-resistant HBV (IC 50 : 3.30 µM) than lamivudine (3TC, IC 50 : 7.37 µM in wild-type HBV, IC 50 : >440 µM in drug-resistant HBV). The antiviral effect of IMB-0523 against HBV may be due to an increased level of intracellular A3G. IMB-0523 also showed low acute toxicity (LD 50 : 448 mg/kg) in mice and promising PK properties (AUC 0-t : 7535.10±2226.73 µg·h/L) in rats. Further, IMB-0523 showed potent anti-HBV activity in DHBV-infected ducks. Conclusion Thus, IMB-0523 may be a potential anti-HBV agent with different mechanisms than current anti-HBV treatment options.

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Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

Cited by 2 publications

References 29 publications

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

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

<p>Synthesis and Bioactivity of <em>N</em>-(4-Chlorophenyl)-4-Methoxy-3-(Methylamino) Benzamide as a Potential Anti-HBV Agent</p>

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