2. Academic Validation
  3. Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2

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

  • Bioorg Med Chem. 2021 Nov 15;50:116454. doi: 10.1016/j.bmc.2021.116454.
Szu Lee 1,  Shih-Wei Wang 2,  Chen-Lin Yu 3,  Huai-Ching Tai 4,  Juei-Yu Yen 3,  Yu-Lien Tuan 3,  Hsueh-Hsiao Wang 5,  Yi-Ting Liu 1,  Shiou-Sheng Chen 6,  Hsueh-Yun Lee 7
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
  • 2 Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 3 Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
  • 4 School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; Department of Urology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan.
  • 5 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
  • 6 Division of Urology, Taipei City Hospital Zhong Xiao Branch, Taipei, Taiwan; Commission for General Education, National Taiwan University of Science and Technology, Taipei, Taiwan; Department of Urology, College of Medicine and Shu-Tien Urological Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; General Education Center, University of Taipei, Taipei, Taiwan. Electronic address: [email protected].
  • 7 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taiwan; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 34634618 DOI: 10.1016/j.bmc.2021.116454
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.

Keywords

HDAC; Phenylurea; VEGFR-2.

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