Abstract

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.

Details

Title
Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK
Author
Li, Hongting 1 ; Mei-Qi Jia 2 ; Zhao-Long, Qin 3 ; Lu, Changliang 4 ; Chu, Weili 5 ; Zhang, Ze 5 ; Niu, Jinbo 6 ; Song, Jian 2 ; Sai-Yang, Zhang 2   VIAFID ORCID Logo  ; 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 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
ISSN
14756366
e-ISSN
14756374
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/14756366.2024.2423875
ProQuest document ID
3149476916
Copyright
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.