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

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. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

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. Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2. Bioorganic & medicinal chemistry. 2021 Nov 15;50:116454

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PMID: 34634618

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