Abstract

We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.

Original languageEnglish
Pages (from-to)10226-10235
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume13
Issue number40
DOIs
Publication statusPublished - Aug 17 2015

Fingerprint

HCT116 Cells
Histone Deacetylase Inhibitors
Histone Deacetylases
Oncology
Poisons
Caspases
inhibitors
Inhibitory Concentration 50
Tumors
Colorectal Neoplasms
cancer
Apoptosis
Derivatives
cells
furans
Neoplasms
apoptosis
cleavage
induction
tendencies

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Biochemistry

Cite this

Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells. / Liu, Yi-Min; Lee, Hsueh Yun; Lai, Mei-Jung; Pan, Shiow Lin; Huang, Hsiang-Ling; Kuo, Fei-Chiao; Chen, Mei Chuan; Liou, Jing Ping.

In: Organic and Biomolecular Chemistry, Vol. 13, No. 40, 17.08.2015, p. 10226-10235.

Research output: Contribution to journalArticle

@article{68588aefcb6246769e9eb29310174ab4,
title = "Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells",
abstract = "We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.",
author = "Yi-Min Liu and Lee, {Hsueh Yun} and Mei-Jung Lai and Pan, {Shiow Lin} and Hsiang-Ling Huang and Fei-Chiao Kuo and Chen, {Mei Chuan} and Liou, {Jing Ping}",
year = "2015",
month = "8",
day = "17",
doi = "10.1039/c5ob01509j",
language = "English",
volume = "13",
pages = "10226--10235",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "40",

}

TY - JOUR

T1 - Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells

AU - Liu, Yi-Min

AU - Lee, Hsueh Yun

AU - Lai, Mei-Jung

AU - Pan, Shiow Lin

AU - Huang, Hsiang-Ling

AU - Kuo, Fei-Chiao

AU - Chen, Mei Chuan

AU - Liou, Jing Ping

PY - 2015/8/17

Y1 - 2015/8/17

N2 - We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.

AB - We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.

UR - http://www.scopus.com/inward/record.url?scp=84944088728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944088728&partnerID=8YFLogxK

U2 - 10.1039/c5ob01509j

DO - 10.1039/c5ob01509j

M3 - Article

C2 - 26309122

AN - SCOPUS:84944088728

VL - 13

SP - 10226

EP - 10235

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 40

ER -