Synthesis and Biological Evaluation of 1-(2-Aminophenyl)-3-arylurea Derivatives as Potential EphA2 and HDAC Dual Inhibitors.

Abstract

A series of 1-(2-aminophenyl)-3-arylurea novel derivatives were synthesized and evaluated against Ephrin type-A receptor 2 (EphA2) and histone deacetylases (HDACs) kinase. Most of the compounds exhibited inhibitory activity against EphA2 and HDAC. The antiproliferative activities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (thiazolyl blue, tetrazolium blue) against the human cancer cell lines HCT116, K562 and MCF7. Compounds 5a and b showed the most potent inhibitory activity against EphA2 and HDAC. However, compound 5b exhibited higher potency against HCT116 (IC50=5.29 µM) and MCF7 (IC50=7.42 µM). 1-(2-Aminophenyl)-3-arylurea analogues may serve as new EphA2-HDAC dual inhibitors.

• Authors: Yong Zhu, Ting Ran, Xin Chen, Jiaqi Niu, Shuang Zhao, Tao Lu, Weifang Tang
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 64 Issue 8 Pg. 1136-41 ( 2016) ISSN: 1347-5223 [Electronic] Japan
• PMID: 27477652 (Publication Type: Journal Article)

Chemical References

• Aniline Compounds
• Antineoplastic Agents
• Enzyme Inhibitors
• Histone Deacetylase Inhibitors
• Urea
• Receptor, EphA2
• Histone Deacetylases

Topics

• Aniline Compounds (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Enzyme Inhibitors (chemical synthesis, chemistry, pharmacology)
• HCT116 Cells
• Histone Deacetylase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Histone Deacetylases (metabolism)
• Humans
• K562 Cells
• MCF-7 Cells
• Molecular Docking Simulation
• Molecular Structure
• Receptor, EphA2 (antagonists & inhibitors, metabolism)
• Structure-Activity Relationship
• Urea (chemical synthesis, chemistry, pharmacology)