2. Academic Validation
  3. Design and synthesis of novel quinazolinone derivatives as anti-HBV agents with TLR8 agonist effect

Design and synthesis of novel quinazolinone derivatives as anti-HBV agents with TLR8 agonist effect

  • Eur J Med Chem. 2022 Mar 5;231:114159. doi: 10.1016/j.ejmech.2022.114159.
Jingying Qiu 1,  Qingqing Zhou 2,  Yueting Zou 2,  Shuqiong Li 2,  Lihua Yang 2,  Wang Chen 2,  Jian Gao 3,  Xiaoke Gu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China; Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
  • 2 Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
  • 3 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China. Electronic address: gaojian@xzhmu.edu.cn.
  • 4 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China. Electronic address: gu_xk@xzhmu.edu.cn.
PMID: 35123297 DOI: 10.1016/j.ejmech.2022.114159
Abstract

Hepatitis B virus (HBV) Infection is a worldwide threat to public health. In this work, a series of novel quinazolinone derivatives (5a-q) were synthesized and evaluated as novel anti-HBV agents. Among them, compound 5l exhibited potent inhibitory effect on HBV DNA replication in both wild type and drug resistant (lamivudine and entecavir) HBV strains with IC50 values of 0.15 and 0.10 μM, respectively. Notably, the selective index value of 5l was high above 66.67, indicating the favorable safety profile. Molecular docking study indicated that compound 5l well fitted into the binding pocket of TLR8 protein-protein interface. Dual-luciferase reporter gene assay further confirmed that compound 5l could dose-dependently activate TLR8, thus effectively inducing the activity of TLR8-dependent NF-κB. Collectively, compound 5l displayed potent anti-HBV activities and TLR8 Agonist effect in vitro, and might be a potential immunomodulatory anti-HBV agent to warrant further investigation.

Keywords

Anti-HBV agents; Quinazolinone derivatives; Synthesis; TLR8 agonist.

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