2. Academic Validation
  3. 2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K

2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K

  • Eur J Med Chem. 2019 Jun 15:172:36-47. doi: 10.1016/j.ejmech.2019.03.030.
Er-Dong Li 1,  Qiao Lin 1,  Ya-Qi Meng 1,  Lu-Ye Zhang 1,  Pan-Pan Song 1,  Na Li 1,  Jing-Chao Xin 1,  Peng Yang 1,  Chong-Nan Bao 1,  Dan-Qing Zhang 1,  Yang Zhang 1,  Ji-Kuan Wang 1,  Qiu-Rong Zhang 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China. Electronic address: zqr409@yeah.net.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
PMID: 30939352 DOI: 10.1016/j.ejmech.2019.03.030
Abstract

A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human Cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MTT assay. Among them, compound 9n showed the most potent cytotoxicity against breast Cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Meanwhile, compound 9n induced cell cycle arrest at G1 phase and cell Apoptosis, as well as increased accumulation of intracellular ROS. Furthermore, compound 9n exerted anti-tumor effects in vitro via decreasing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 9n markedly decreased p-EGFR and p-PI3K expression, which revealed that compound 9n targeted breast Cancer cells via interfering with EGFR-PI3K signaling pathway. Molecular docking suggested that compound 9n could indeed bind into the active pocket of EGFR. All the findings suggest that compound 9n might be a valuable lead compound for anti-tumor agents targeting breast Cancer cells.

Keywords

Breast cancer; EGFR-PI3K; Quinazoline.

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