Antimitotic and vascular disrupting agents: 2-Hydroxy-3,4,5- trimethoxybenzophenones

Chih Yi Chang, Hsun Yueh Chuang, Hsueh Yun Lee, Teng Kuang Yeh, Ching Chuan Kuo, Chi Yen Chang, Jang Yang Chang, Jing Ping Liou

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.

Original languageEnglish
Pages (from-to)306-314
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume77
DOIs
Publication statusPublished - Apr 22 2014

Fingerprint

Benzophenones
Antimitotic Agents
KB Cells
Endothelial cells
Human Umbilical Vein Endothelial Cells
Hydrogen Bonding
Tubulin
Blood Vessels
Hydrogen bonds
(3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)methanone
fosbretabulin

Keywords

  • Antiproliferative
  • CA-4
  • Vascular-disrupting agents

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

Antimitotic and vascular disrupting agents : 2-Hydroxy-3,4,5- trimethoxybenzophenones. / Chang, Chih Yi; Chuang, Hsun Yueh; Lee, Hsueh Yun; Yeh, Teng Kuang; Kuo, Ching Chuan; Chang, Chi Yen; Chang, Jang Yang; Liou, Jing Ping.

In: European Journal of Medicinal Chemistry, Vol. 77, 22.04.2014, p. 306-314.

Research output: Contribution to journalArticle

Chang, Chih Yi ; Chuang, Hsun Yueh ; Lee, Hsueh Yun ; Yeh, Teng Kuang ; Kuo, Ching Chuan ; Chang, Chi Yen ; Chang, Jang Yang ; Liou, Jing Ping. / Antimitotic and vascular disrupting agents : 2-Hydroxy-3,4,5- trimethoxybenzophenones. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 77. pp. 306-314.
@article{0edb19bf4a3d40e4abe1a087d4285457,
title = "Antimitotic and vascular disrupting agents: 2-Hydroxy-3,4,5- trimethoxybenzophenones",
abstract = "2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.",
keywords = "Antiproliferative, CA-4, Vascular-disrupting agents",
author = "Chang, {Chih Yi} and Chuang, {Hsun Yueh} and Lee, {Hsueh Yun} and Yeh, {Teng Kuang} and Kuo, {Ching Chuan} and Chang, {Chi Yen} and Chang, {Jang Yang} and Liou, {Jing Ping}",
year = "2014",
month = "4",
day = "22",
doi = "10.1016/j.ejmech.2014.02.061",
language = "English",
volume = "77",
pages = "306--314",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Antimitotic and vascular disrupting agents

T2 - 2-Hydroxy-3,4,5- trimethoxybenzophenones

AU - Chang, Chih Yi

AU - Chuang, Hsun Yueh

AU - Lee, Hsueh Yun

AU - Yeh, Teng Kuang

AU - Kuo, Ching Chuan

AU - Chang, Chi Yen

AU - Chang, Jang Yang

AU - Liou, Jing Ping

PY - 2014/4/22

Y1 - 2014/4/22

N2 - 2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.

AB - 2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.

KW - Antiproliferative

KW - CA-4

KW - Vascular-disrupting agents

UR - http://www.scopus.com/inward/record.url?scp=84896536146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896536146&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2014.02.061

DO - 10.1016/j.ejmech.2014.02.061

M3 - Article

C2 - 24657567

AN - SCOPUS:84896536146

VL - 77

SP - 306

EP - 314

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -