Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer
A series of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives were designed and synthesised as novel fibroblast growth factor receptor-1 (FGFR1) inhibitors. We found that one of the most promising compounds, C9, inhibited five non-small cell lung cancer (NSCLC) cell lines with FGFR1 amplification...
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doaj-08f37696aafd42ddb78e75713178361f2020-11-25T02:01:55ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-0133190591910.1080/14756366.2018.14608241460824Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancerZixin Xie0Donghua Cheng1Lu Luo2Guoliang Shen3Suwei Pan4Yaqian Pan5Bo Chen6Xuebao Wang7Zhiguo Liu8Yuan Zhang9Faqing Ye10Wenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityWenzhou Medical UniversityA series of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives were designed and synthesised as novel fibroblast growth factor receptor-1 (FGFR1) inhibitors. We found that one of the most promising compounds, C9, inhibited five non-small cell lung cancer (NSCLC) cell lines with FGFR1 amplification, including NCI-H520, NCI-H1581, NCI-H226, NCI-H460 and NCI-H1703. Moreover, the IC50 values for the compound C9 were 1.36 ± 0.27 µM, 1.25 ± 0. 23 µM, 2.31 ± 0.41 µM, 2.14 ± 0.36 µM and 1.85 ± 0.32 µM, respectively. The compound C9 arrested the cell cycle at the G2 phase in NSCLC cell lines. The compound C9 also induced cellular apoptosis and inhibited the phosphorylation of FGFR1, PLCγ1 and ERK in a dose-dependent manner. In addition, molecular docking experiments showed that compound C9 binds to FGFR1 to form six hydrogen bonds. Taken together, our data suggested that the compound C9 represented a promising lead compound-targeting FGFR1.http://dx.doi.org/10.1080/14756366.2018.1460824Benzamide derivativesFGFR1inhibitorsmolecular dockingNSCLC |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zixin Xie Donghua Cheng Lu Luo Guoliang Shen Suwei Pan Yaqian Pan Bo Chen Xuebao Wang Zhiguo Liu Yuan Zhang Faqing Ye |
spellingShingle |
Zixin Xie Donghua Cheng Lu Luo Guoliang Shen Suwei Pan Yaqian Pan Bo Chen Xuebao Wang Zhiguo Liu Yuan Zhang Faqing Ye Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer Journal of Enzyme Inhibition and Medicinal Chemistry Benzamide derivatives FGFR1 inhibitors molecular docking NSCLC |
author_facet |
Zixin Xie Donghua Cheng Lu Luo Guoliang Shen Suwei Pan Yaqian Pan Bo Chen Xuebao Wang Zhiguo Liu Yuan Zhang Faqing Ye |
author_sort |
Zixin Xie |
title |
Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer |
title_short |
Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer |
title_full |
Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer |
title_fullStr |
Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer |
title_full_unstemmed |
Design, synthesis and biological evaluation of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives as novel FGFR1 inhibitors for treatment of non-small cell lung cancer |
title_sort |
design, synthesis and biological evaluation of 4-bromo-n-(3,5-dimethoxyphenyl)benzamide derivatives as novel fgfr1 inhibitors for treatment of non-small cell lung cancer |
publisher |
Taylor & Francis Group |
series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
issn |
1475-6366 1475-6374 |
publishDate |
2018-01-01 |
description |
A series of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives were designed and synthesised as novel fibroblast growth factor receptor-1 (FGFR1) inhibitors. We found that one of the most promising compounds, C9, inhibited five non-small cell lung cancer (NSCLC) cell lines with FGFR1 amplification, including NCI-H520, NCI-H1581, NCI-H226, NCI-H460 and NCI-H1703. Moreover, the IC50 values for the compound C9 were 1.36 ± 0.27 µM, 1.25 ± 0. 23 µM, 2.31 ± 0.41 µM, 2.14 ± 0.36 µM and 1.85 ± 0.32 µM, respectively. The compound C9 arrested the cell cycle at the G2 phase in NSCLC cell lines. The compound C9 also induced cellular apoptosis and inhibited the phosphorylation of FGFR1, PLCγ1 and ERK in a dose-dependent manner. In addition, molecular docking experiments showed that compound C9 binds to FGFR1 to form six hydrogen bonds. Taken together, our data suggested that the compound C9 represented a promising lead compound-targeting FGFR1. |
topic |
Benzamide derivatives FGFR1 inhibitors molecular docking NSCLC |
url |
http://dx.doi.org/10.1080/14756366.2018.1460824 |
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