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In this work, thirty 2,4-diarylaminopyrimidine-based hydrazones were designed, synthesised, and their anti-thyroid cancer activity were explored. The majority of compounds exhibit moderate to excellent cytotoxic activity against FAK overexpressing TPC-1 cells, with IC50 values ranging from 0.113 to 1.460 μM. Among them, compound 14f displayed exceptional anti-proliferative effect against TPC-1 cells (IC50 = 0.113 μM) and potent FAK inhibitory potency (IC50 = 35 nM). In silico studies indicated that compound 14f could well bind to FAK (Focal Adhesion Kinase) and have favourable pharmacokinetic profiles. In addition, compound 14f could inhibit the phosphorylation of FAK at Tyr397, Tyr576/577 and Tyr925, and did not affect the expression level of FAK in TPC-1 cells. Compound 14f was also effective in inhibiting the proliferation and migration of thyroid cancer cells TPC-1. Thus, these novel 4-arylaminopyrimidine hydrazone derivatives exhibited potent anti-thyroid cancer activities through the inhibition of FAK.
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; Fu, Lijun 1 1 Department of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
2 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
3 School of Pharmaceutical Sciences, Institute of Drug Discovery & Development Key, Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou, Henan Province, China
4 Zhengzhou Xingyuan Foreign Language High School, Zhengzhou, Henan Province, China
5 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
6 The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China