Citation: Hong-Xia LI, Yu-Mei QIAN, Li-Sheng XU. Design, Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors[J]. Chinese Journal of Structural Chemistry, ;2021, 40(7): 933-941. doi: 10.14102/j.cnki.0254–5861.2011–3082 shu

Design, Synthesis and Anticancer Activity Evaluation of Novel Quinazoline Derivatives as EFGR Inhibitors

School of Life and Food Engineering, Suzhou University, Suzhou 234000, China

Corresponding author: Hong-Xia LI, szxy2016hx@163.com
Received Date: 28 December 2020
Accepted Date: 12 March 2021

Fund Project: the Suzhou University Natural Science Key Project 2017yzd11the Suzhou University Natural Science Key Project 2020ykf23the Suzhou University Natural Science Key Project 2020ykf24National Engineering Laboratory Open Fund Project NEL-SCRT 002Natural Science Foundation of An Hui Province 1908085MC100Natural Science Foundation of An Hui Province KJ2020A0729Natural Science Foundation of An Hui Province KJ2020A0737

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Malignant tumor is one of the major diseases that seriously threaten human health today. Compared with traditional chemotherapy, targeted drug therapy has become a new idea of tumor therapy. And EGFR (epidermal growth factor receptor) is highly expressed in many human tumor cell lines, which is a biomarker of tumor proliferation. In this paper, small molecule tyrosine kinase inhibitors with quinazoline structure aiming at EGFR were studied. A series of novel quinazoline derivatives (4a~4l) have been designed and synthesized from 4-hydroxyquinazoline as the parent core. Structures of target compounds were characterized by ¹H NMR and ¹³C NMR spectra. The in vitro anticancer activity of compounds 4a~4l was evaluated by MTT assay against Hela, MCF-7 and A549 tumor cell lines, and apoptosis-inducing capacity was investigated by Annexin-V/PI staining assay. The results showed that all compounds had good antitumor activity against the test tumor cell lines. Especially, compound 4a exhibited the best anticancer activity (IC₅₀ = 10.23 μM) against Hela cell lines, remarkable ability to induce apoptosis, and low toxicity, which identified 4a as a promising anticancer drug aiming at EFGR.
- hydroxyquinazoline,
- EFGR,
- antitumor activity,
- toxicity,
- apoptosis
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