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

doi:10.1016/j.bmc.2021.116454

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 journal › Article › peer-review

1 Citation (Scopus)

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 language	English
Article number	116454
Journal	Bioorganic and Medicinal Chemistry
Volume	50
DOIs	https://doi.org/10.1016/j.bmc.2021.116454
Publication status	Published - 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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10.1016/j.bmc.2021.116454

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title = "Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2",

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",

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

note = "Funding Information: This research was supported by the Ministry of Science and Technology, Taiwan (grant no. MOST108-2320-B-038-042-MY3 and MOST 110-2628-B-715-001). MacKay Medical College (grant no. MMC-RD-109-CF-G2-03), Taiwan. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

year = "2021",

month = nov,

day = "15",

doi = "10.1016/j.bmc.2021.116454",

language = "English",

volume = "50",

journal = "Bioorganic and Medicinal Chemistry",

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T1 - Effect of phenylurea hydroxamic acids on histone deacetylase and VEGFR-2

AU - Lee, Szu

AU - Wang, Shih Wei

AU - Yu, Chen Lin

AU - Tai, Huai Ching

AU - Yen, Juei Yu

AU - Tuan, Yu Lien

AU - Wang, Hsueh Hsiao

AU - Liu, Yi Ting

AU - Chen, Shiou Sheng

AU - Lee, Hsueh Yun

N1 - Funding Information: This research was supported by the Ministry of Science and Technology, Taiwan (grant no. MOST108-2320-B-038-042-MY3 and MOST 110-2628-B-715-001). MacKay Medical College (grant no. MMC-RD-109-CF-G2-03), Taiwan. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/11/15

Y1 - 2021/11/15

N2 - 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.

AB - 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.

KW - HDAC

KW - Phenylurea

KW - VEGFR-2

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DO - 10.1016/j.bmc.2021.116454

M3 - Article

AN - SCOPUS:85116596381

SN - 0968-0896

VL - 50

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

M1 - 116454

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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