2. Academic Validation
  3. Hybrids from 4-anilinoquinazoline and hydroxamic acid as dual inhibitors of vascular endothelial growth factor receptor-2 and histone deacetylase

Hybrids from 4-anilinoquinazoline and hydroxamic acid as dual inhibitors of vascular endothelial growth factor receptor-2 and histone deacetylase

  • Bioorg Med Chem Lett. 2015 Nov 15;25(22):5137-41. doi: 10.1016/j.bmcl.2015.10.006.
Fan-Wei Peng 1,  Ting-Ting Wu 1,  Zi-Wei Ren 1,  Jia-Yu Xue 2,  Lei Shi 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: shilei@cpu.edu.cn.
PMID: 26475519 DOI: 10.1016/j.bmcl.2015.10.006
Abstract

A series of hybrids derived from 4-anilinoquinazoline and hydroxamic acid were designed, synthesized, and evaluated as dual inhibitors of vascular endothelia growth factor receptor-2 (VEGFR-2) tyrosine kinase and histone deacetylase (HDAC). Most of these compounds exhibited potent HDAC inhibition and moderate VEGFR-2 inhibition. Among them, compound 6l exhibited the most potent inhibitory activities against VEGFR-2 (IC50=84 nM) and HDAC (IC50=2.8 nM). It also showed the most potent antiproliferative ability against MCF-7, a human breast Cancer line, with IC50 of 1.2 μM. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction of compound 6l at the active binding sites of VEGFR-2 and HDAC.

Keywords

4-Anilinoquinazoline; HDAC; Hybrid; Hydroxamic acid; VEGFR-2.

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