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

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2018 May 9

PMID 29734851

Citations 4

Authors

Zixin Xie

Donghua Cheng

Lu Luo

Guoliang Shen

Suwei Pan

Yaqian Pan

Bo Chen

Xuebao Wang

Zhiguo Liu

Yuan Zhang

Faqing Ye

Affiliations

Soon will be listed here.

Abstract

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 IC 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.

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