Synthesis and Bioactivity of N

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 jV-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 V-phenylbenzamide derivatives against HBV. Methods: In this study, a new derivative, V-(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 (I[C.sub.50]: 1.99 [micro]M) and drug-resistant HBV (I[C.sub.50]: 3.30 [micro]M) than lamivudine (3TC, I[C.sub.50]: 7.37 [micro]M in wild-type HBV, I[C.sub.50]: >440 [micro]M 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 (LD50: 448 mg/kg) in mice and promising PK properties (AU[C.sub.0-t]: 7535.10[+ or -]2226.73 [micro]gfi/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. Keywords: anti-HBV activity, APOBEC3G, hepatitis B virus, IMB-0523, PK, toxicity