Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK

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Publicado en:Journal of Enzyme Inhibition and Medicinal Chemistry vol. 39, no. 1 (Dec 2024)
Autor principal: Li, Hongting
Otros Autores: Mei-Qi Jia, Zhao-Long, Qin, Lu, Changliang, Chu, Weili, Zhang, Ze, Niu, Jinbo, Song, Jian, Sai-Yang, Zhang, Fu, Lijun
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Taylor & Francis Ltd.
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Acceso en línea:Citation/Abstract
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022 |a 1475-6366 
022 |a 1475-6374 
022 |a 8755-5093 
024 7 |a 10.1080/14756366.2024.2423875  |2 doi 
035 |a 3149476916 
045 2 |b d20241201  |b d20241231 
100 1 |a Li, Hongting  |u Department of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 
245 1 |a Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK 
260 |b Taylor & Francis Ltd.  |c Dec 2024 
513 |a Journal Article 
520 3 |a 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. 
653 |a Cytotoxicity 
653 |a Cell migration 
653 |a Thyroid cancer 
653 |a Phosphorylation 
653 |a Pharmacokinetics 
653 |a Focal adhesion kinase 
653 |a Cell proliferation 
653 |a Thyroidectomy 
653 |a Hydrogen bonds 
653 |a Pharmaceutical sciences 
653 |a Cancer therapies 
653 |a Clinical trials 
653 |a Chemistry 
653 |a Design 
653 |a Enzymes 
653 |a Kinases 
700 1 |a Mei-Qi Jia  |u School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China 
700 1 |a Zhao-Long, Qin  |u 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 
700 1 |a Lu, Changliang  |u Zhengzhou Xingyuan Foreign Language High School, Zhengzhou, Henan Province, China 
700 1 |a Chu, Weili  |u Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 
700 1 |a Zhang, Ze  |u Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 
700 1 |a Niu, Jinbo  |u The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China 
700 1 |a Song, Jian  |u School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China 
700 1 |a Sai-Yang, Zhang  |u School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China 
700 1 |a Fu, Lijun  |u Department of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China 
773 0 |t Journal of Enzyme Inhibition and Medicinal Chemistry  |g vol. 39, no. 1 (Dec 2024) 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3149476916/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3149476916/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch