1. Academic Validation
  2. Protective effects of 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates on vascular cognitive impairment

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

  • Eur J Med Chem. 2020 Feb 1;187:111915. doi: 10.1016/j.ejmech.2019.111915.
Navdeep Kaur 1 Yao-Ching Fang 2 Hsueh-Yun Lee 1 Arshdeep Singh 1 Kunal Nepali 1 Mei-Hsiang Lin 1 Teng-Kuang Yeh 3 Mei-Jung Lai 4 Lung Chan 5 Yong-Kwang Tu 6 Suddhasatwa Banerjee 1 Chaur-Jong Hu 7 Jing-Ping Liou 8
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
  • 2 Taipei Neuroscience Institute, Taipei Medical University, Taiwan.
  • 3 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institute, Zhunan Town, Miaoli County, Taiwan.
  • 4 TMU Biomedical Commercialization Center, Taipei Medical University, Taiwan.
  • 5 Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
  • 6 Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Taipei Neuroscience Institute, Taipei Medical University, Taiwan.
  • 7 Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Taipei Neuroscience Institute, Taipei Medical University, Taiwan. Electronic address: chaurjongh@tmu.edu.tw.
  • 8 School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan; TMU Biomedical Commercialization Center, Taipei Medical University, Taiwan. Electronic address: jpl@tmu.edu.tw.
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.

Figures
Products