摘要

A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4–15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.
原文英語
文章編號111915
期刊European Journal of Medicinal Chemistry
187
DOIs
出版狀態已發佈 - 二月 1 2020

指紋

Azepines
Histone Deacetylase Inhibitors
Blood Vessels
Acetylation
Acrylamide
Cerebrovascular Circulation
Histones
Blood
Atrophy
Dementia
Hippocampus
Cognitive Dysfunction

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

引用此文

@article{3eb10cf80a7549f39528aaaddae60522,
title = "Protective effects of 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates on vascular cognitive impairment",
abstract = "A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4–15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.",
keywords = "Histone deacetylase inhibitors, Neurodegenerative disease, Vascular cognitive impairment",
author = "Navdeep Kaur and Fang, {Yao Ching} and Lee, {Hsueh Yun} and Arshdeep Singh and Kunal Nepali and Lin, {Mei Hsiang} and Yeh, {Teng Kuang} and Lai, {Mei Jung} and Lung Chan and Tu, {Yong Kwang} and Suddhasatwa Banerjee and Hu, {Chaur Jong} and Liou, {Jing Ping}",
year = "2020",
month = "2",
day = "1",
doi = "10.1016/j.ejmech.2019.111915",
language = "English",
volume = "187",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Protective effects of 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates on vascular cognitive impairment

AU - Kaur, Navdeep

AU - Fang, Yao Ching

AU - Lee, Hsueh Yun

AU - Singh, Arshdeep

AU - Nepali, Kunal

AU - Lin, Mei Hsiang

AU - Yeh, Teng Kuang

AU - Lai, Mei Jung

AU - Chan, Lung

AU - Tu, Yong Kwang

AU - Banerjee, Suddhasatwa

AU - Hu, Chaur Jong

AU - Liou, Jing Ping

PY - 2020/2/1

Y1 - 2020/2/1

N2 - A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4–15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.

AB - A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4–15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.

KW - Histone deacetylase inhibitors

KW - Neurodegenerative disease

KW - Vascular cognitive impairment

UR - http://www.scopus.com/inward/record.url?scp=85076133362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076133362&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2019.111915

DO - 10.1016/j.ejmech.2019.111915

M3 - Article

AN - SCOPUS:85076133362

VL - 187

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

M1 - 111915

ER -