2. Academic Validation
  3. Optimization and biological evaluation of nicotinamide derivatives as Aurora kinase inhibitors

Optimization and biological evaluation of nicotinamide derivatives as Aurora kinase inhibitors

  • Bioorg Med Chem. 2019 Sep 1;27(17):3825-3835. doi: 10.1016/j.bmc.2019.07.016.
Baohui Qi 1,  Xingwei Xu 2,  Ying Yang 2,  Huan He 2,  Xupeng Yue 2
Affiliations

Affiliations

  • 1 Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China. Electronic address: bhqi@zmu.gd.cn.
  • 2 Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China.
PMID: 31307762 DOI: 10.1016/j.bmc.2019.07.016
Abstract

Aurora kinases are known to be overexpressed in various solid tumors and implicated in oncogenesis and tumor progression. A series of nicotinamide derivatives were synthesized and their biological activities were evaluated, including kinase inhibitory activity against Aur A and Aur B and in vitro antitumor activity against SW620, HT-29, NCI-H1975 and Hela Cancer cell lines. In addition, the study of antiproliferation, cytotoxicity and Apoptosis was performed meanwhile. As the most potent inhibitor of Aur A, 4-((3-bromo-4-fluorophenyl)amino)-6-chloro-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)nicotinamide (10l) showed excellent antitumor activity against SW620 and NCI-H1975 with IC50 values were 0.61 and 1.06 μM, while the IC50 values of reference compound were 3.37 and 6.67 μM, respectively. Furthermore, binding mode studies indicated that compound 10l forms better interaction with Aur A.

Keywords

Antitumor; Aurora kinases; Kinase inhibitors; Nicotinamide; SAR.

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