2. Academic Validation
  3. Discovery of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives as potential anticancer agents by inhibiting cell proliferation and inducing apoptosis in hepatocellular carcinoma cells

Discovery of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives as potential anticancer agents by inhibiting cell proliferation and inducing apoptosis in hepatocellular carcinoma cells

  • Eur J Med Chem. 2021 Nov 15:224:113671. doi: 10.1016/j.ejmech.2021.113671.
Chao-Jie Wang 1,  Xinxin Guo 1,  Rui-Qin Zhai 1,  Changning Sun 1,  Guokai Xiao 1,  Jin Chen 1,  Mei-Yan Wei 2,  Chang-Lun Shao 3,  Yuchao Gu 4
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, People's Republic of China.
  • 2 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, People's Republic of China; College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, People's Republic of China.
  • 3 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, People's Republic of China. Electronic address: shaochanglun@163.com.
  • 4 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, People's Republic of China. Electronic address: guych@126.com.
PMID: 34237623 DOI: 10.1016/j.ejmech.2021.113671
Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver Cancer and the fourth leading cause of cancer-related death worldwide. First-line drugs such as sorafenib provide only a modest benefit to HCC patients. In this study, the gram-scale synthesis of 2-benzoylquinazolin-4(3H)-one skeleton was achieved successfully via the I2/DMSO catalytic system. A series of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives was synthesized and evaluated for their cytotoxic activities against four Cancer cell lines, HepG2, Bel-7402, A549, and U251. Among these compounds, 4a was the most effective one with IC50 values of 1.22 μM and 1.71 μM against HepG2 and Bel-7402 cells, respectively. Mechanistic studies showed that 4a inhibited hepatocellular carcinoma cell proliferation via arresting cell cycle. Additionally, 4a induced HepG2 cells Apoptosis by inducing Reactive Oxygen Species production and elevating the expression of apoptosis-related proteins. More importantly, 4a displayed significant in vivo Anticancer effects in the HepG2 xenograft models. This suggests that 4a is a promising lead compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.

Keywords

Apoptosis; Cell cycle; Hepatocellular carcinoma; Penipanoid C; Quinazoline.

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