Novel conjugates of endoperoxide and 4-anilinoquinazoline as potential anticancer agents

  • Bioorg Med Chem Lett. 2017 Mar 15;27(6):1341-1345. doi: 10.1016/j.bmcl.2017.02.023.
Jing Yang  1 ,  Zhengchao Tu  2 ,  Xin Xu  1 ,  Jinfeng Luo  2 ,  Xing Yan  1 ,  Chongzhao Ran  3 ,  Xinliang Mao  1 ,  Ke Ding  4 ,  Chunhua Qiao  5
Affiliations
  • 1. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China.
  • 2. Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, China.
  • 3. Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Building 75, Charlestown, MA 02129, United States.
  • 4. Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou 510530, China. Electronic address: [email protected].
  • 5. College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, China. Electronic address: [email protected].
PMID: 28236592 DOI: 10.1016/j.bmcl.2017.02.023
Abstract

In the present study, endoperoxide and 4-anilinoqnazoline were conjugated to obtain a series of compounds. These conjugates exhibited high antiproliferative potency against a number of Cancer cell lines, including the epidermal growth factor receptor (EGFR) L858R/T790M mutant cell. Compound 5 was selected as a representative for mechanistic study. Further experiments revealed the conjugate's Reactive Oxygen Species (ROS) generating ability, Apoptosis inducing activity and involvement in EGFR downstream signaling pathways.

Keywords
4-Anilinoquinazoline; Anti-cancer agents; Conjugates; EGFR-TKI; Endoperoxide.