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  3. Discovery of novel quinazolinone derivatives as potential anti-HBV and anti-HCC agents

Discovery of novel quinazolinone derivatives as potential anti-HBV and anti-HCC agents

  • Eur J Med Chem. 2020 Nov 1;205:112581. doi: 10.1016/j.ejmech.2020.112581.
Jingying Qiu 1,  Qingqing Zhou 2,  Yinpeng Zhang 2,  Mingyu Guan 3,  Xin Li 3,  Yueting Zou 2,  Xuan Huang 3,  Yali Zhao 3,  Wang Chen 2,  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.
  • 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: 32791397 DOI: 10.1016/j.ejmech.2020.112581
Abstract

As a continuation of earlier works, a series of novel quinazolinone derivatives (5a-s) were synthesized and evaluated for their in vitro anti-HBV and anti-hepatocellular carcinoma cell (HCC) activities. Among them, compounds 5j and 5k exhibited most potent inhibitory effect on HBV DNA replication in both drug sensitive and resistant (lamivudine and entecavir) HBV strains. Interestingly, besides the anti-HBV effect, compound 5k could significantly inhibit the proliferation of HepG2, HUH7 and SK- cells, with IC50 values of 5.44, 6.42 and 6.75 μM, respectively, indicating its potential anti-HCC activity. Notably, the in vitro anti-HCC activity of 5k were more potent than that of positive control 5-fluorouracil and sorafenib. Further studies revealed that compound 5k could induce HepG2 cells Apoptosis by dose-dependently upregulating Bad and Bax expression and decreasing Bcl-2 and Bcl-xL protein level. Considering the potent anti-HBV and anti-HCC effect, compound 5k might be a promising lead to develop novel therapeutic agents towards HBV Infection and HBV-induced HCC.

Keywords

Anti-HBV agents; Anti-HCC activity; Non-nucleoside; Quinazolinone derivatives.

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