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

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, a...

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Detalles Bibliográficos
Autores principales: Cui, A-Long, Sun, Wen-Fang, Zhong, Zhao-Jin, Jin, Jie, Xue, Si-Tu, Wu, Shuo, Li, Yu-Huan, Li, Zhuo-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501955/
https://www.ncbi.nlm.nih.gov/pubmed/32982177
http://dx.doi.org/10.2147/DDDT.S263701
Descripción
Sumario: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.