Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers
A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activ...
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1518957 |
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doaj-b6667df4acdd496db8d0f8b03a20c1202020-11-25T01:48:50ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-0134120321710.1080/14756366.2018.15189571518957Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancersCaolin Wang0Shan Xu1Liang Peng2Bingliang Zhang3Hong Zhang4Yingying Hu5Pengwu Zheng6Wufu Zhu7Jiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityJiangxi Science & Technology Normal UniversityA series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFRWT with the IC50 value both less than 2 nM. Among the six compounds, 44 exhibited the strongest activity (0.4 nM) and potently inhibited EGFRL858R/T790M (0.1 μM). Excitingly, the most potent compound 14 showed excellent enzyme inhibitory activity with 6.3 nM and 8.4 nM for both EGFRWT and EGFRT790M/L858R. The result of AO single staining and Annexin V/PI staining showed that the compound 14 and 44 could induce remarkable apoptosis of A549 cells. The compound 14 arrested the cell cycle at the S phase and compound 44 arrested the cell cycle at the G0 phase in A549 cells. These preliminary results demonstrate that compound 14 and 44 may be promising lead compound-targeting EGFR.http://dx.doi.org/10.1080/14756366.2018.1518957quinazoline derivativesbenzylidene hydrazinensclcegfrinhibitors |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Caolin Wang Shan Xu Liang Peng Bingliang Zhang Hong Zhang Yingying Hu Pengwu Zheng Wufu Zhu |
| spellingShingle |
Caolin Wang Shan Xu Liang Peng Bingliang Zhang Hong Zhang Yingying Hu Pengwu Zheng Wufu Zhu Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers Journal of Enzyme Inhibition and Medicinal Chemistry quinazoline derivatives benzylidene hydrazine nsclc egfr inhibitors |
| author_facet |
Caolin Wang Shan Xu Liang Peng Bingliang Zhang Hong Zhang Yingying Hu Pengwu Zheng Wufu Zhu |
| author_sort |
Caolin Wang |
| title |
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| title_short |
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| title_full |
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| title_fullStr |
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| title_full_unstemmed |
Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| title_sort |
design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as egfr inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers |
| publisher |
Taylor & Francis Group |
| series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
| issn |
1475-6366 1475-6374 |
| publishDate |
2019-01-01 |
| description |
A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFRWT with the IC50 value both less than 2 nM. Among the six compounds, 44 exhibited the strongest activity (0.4 nM) and potently inhibited EGFRL858R/T790M (0.1 μM). Excitingly, the most potent compound 14 showed excellent enzyme inhibitory activity with 6.3 nM and 8.4 nM for both EGFRWT and EGFRT790M/L858R. The result of AO single staining and Annexin V/PI staining showed that the compound 14 and 44 could induce remarkable apoptosis of A549 cells. The compound 14 arrested the cell cycle at the S phase and compound 44 arrested the cell cycle at the G0 phase in A549 cells. These preliminary results demonstrate that compound 14 and 44 may be promising lead compound-targeting EGFR. |
| topic |
quinazoline derivatives benzylidene hydrazine nsclc egfr inhibitors |
| url |
http://dx.doi.org/10.1080/14756366.2018.1518957 |
| work_keys_str_mv |
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| _version_ |
1725009776021078016 |