Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2

Szu Lee, Shih Wei Wang, Chen Lin Yu, Huai Ching Tai, Juei Yu Yen, Yu Lien Tuan, Hsueh Hsiao Wang, Yi Ting Liu, Shiou Sheng Chen, Hsueh Yun Lee

Research output: Contribution to journalArticlepeer-review

Abstract

A series of phenylurea hydroxamic acids incorporating pharmacophores of inhibitors of HDAC inhibitors and VEGFR-2 has been designed. Most of the compounds show antiproliferative activity comparable to that of Vorinostat and Sorafenib, and better EPC inhibitory activity. Enzymatic assays and Western blotting results indicated that compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A docking study revealed that the polar hydroxamic acid retains the interaction with HDAC through a zinc ion and also interacts with some residues of the active site of VEGFR-2. Despite 14 displaying a weaker VEGFR-2 activity, a possible route to develop potent HDAC/VEGFR-2 inhibitors is suggested.

Original languageEnglish
Article number116454
JournalBioorganic and Medicinal Chemistry
Volume50
DOIs
Publication statusPublished - Nov 15 2021

Keywords

  • HDAC
  • Phenylurea
  • VEGFR-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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