Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes

Hsueh Yun Lee; Chih-Yi Chang; Mei-Jung Lai; Hsun-Yueh Chuang; Ching-Chuan Kuo; Chi-Yen Chang; Jang-Yang Chang; Jing Ping Liou

doi:10.1016/j.bmc.2015.06.043

Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes

Hsueh Yun Lee, Chih-Yi Chang, Mei-Jung Lai, Hsun-Yueh Chuang, Ching-Chuan Kuo, Chi-Yen Chang, Jang-Yang Chang, Jing Ping Liou

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC₅₀ values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.

Original language	English
Pages (from-to)	4230-4236
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	15
DOIs	https://doi.org/10.1016/j.bmc.2015.06.043
Publication status	Published - Jul 23 2015

Keywords

Antiproliferative
CA-4
Vascular-disrupting agents

ASJC Scopus subject areas

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

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10.1016/j.bmc.2015.06.043

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title = "Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes",

abstract = "This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.",

keywords = "Antiproliferative, CA-4, Vascular-disrupting agents",

author = "Lee, {Hsueh Yun} and Chih-Yi Chang and Mei-Jung Lai and Hsun-Yueh Chuang and Ching-Chuan Kuo and Chi-Yen Chang and Jang-Yang Chang and Liou, {Jing Ping}",

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AU - Lee, Hsueh Yun

AU - Chang, Chih-Yi

AU - Lai, Mei-Jung

AU - Chuang, Hsun-Yueh

AU - Kuo, Ching-Chuan

AU - Chang, Chi-Yen

AU - Chang, Jang-Yang

AU - Liou, Jing Ping

PY - 2015/7/23

Y1 - 2015/7/23

N2 - This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.

AB - This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.

KW - Antiproliferative

KW - CA-4

KW - Vascular-disrupting agents

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JO - Bioorganic and Medicinal Chemistry

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IS - 15

ER -

Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes

Abstract

Keywords

ASJC Scopus subject areas

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