Design, synthesis and antiproliferative activity evaluation of EGFR inhibitors containing 3-hydroxy-4-pyridinone fragment

LIU Shen1 SHAO Jia-an2 YU Yong-ping1

(1.Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Science, Zhejiang University, Hangzhou, China 310058)
(2.Department of Chemistry, College of Science, Zhejiang Sci-Tech University, Hangzhou, China 310018)

【Abstract】The development of multi-targeted tyrosine kinase inhibitors is of great significance for anti-cancer therapy. Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in the apoptosis, proliferation, differentiation, migration and cell cycle of cancer cells. Meanwhile, Fe chelators are effective antitumor agents. By incorporating 3-hydroxy-4-pyridinone fragment (a Fe chelator motif) into the conventional quinazoline scaffold of EGFR inhibitors, 12 compounds which may target multiple drug targets were synthesized. The general procedure for the synthesis of target compounds was described and all of them were characterized by 1H-NMR, MS and melting point. In the tumor cell lines tested, most of the compounds exhibit efficient antiproliferative activity on the human epidermal carcinoma cell A431 (with EGFR overexpression) and HeLa, albeit a moderate inhibition in gefitinib-resistant NSCLC cell H1975 (bearing EGFR[L858R/T790M]).

【Keywords】 EGFR tyrosine kinase inhibitor; 4-anilinoquinazoline; 3-hydroxy-4-pyridinone; multiple-target; antiproliferative activity;


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This Article



Vol 27, No. 01, Pages 1-7

February 2017


Article Outline


  • 1 Design of target compounds and synthetic routes
  • 2 Synthetic experiments
  • 3 Antiproliferative activity assay in vitro
  • References