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

Navdeep Kaur; Yao Ching Fang; Hsueh Yun Lee; Arshdeep Singh; Kunal Nepali; Mei Hsiang Lin; Teng Kuang Yeh; Mei Jung Lai; Lung Chan; Yong Kwang Tu; Suddhasatwa Banerjee; Chaur Jong Hu; Jing Ping Liou

doi:10.1016/j.ejmech.2019.111915

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

Navdeep Kaur, Yao Ching Fang, Hsueh Yun Lee, Arshdeep Singh, Kunal Nepali, Mei Hsiang Lin, Teng Kuang Yeh, Mei Jung Lai, Lung Chan, Yong Kwang Tu, Suddhasatwa Banerjee, Chaur Jong Hu, Jing Ping Liou

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14 Citations (Scopus)

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.

Original language	English
Article number	111915
Journal	European Journal of Medicinal Chemistry
Volume	187
DOIs	https://doi.org/10.1016/j.ejmech.2019.111915
Publication status	Published - Feb 1 2020

Keywords

Histone deacetylase inhibitors
Neurodegenerative disease
Vascular cognitive impairment

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2019.111915

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Kaur, N., Fang, Y. C., Lee, H. Y., Singh, A., Nepali, K., Lin, M. H., Yeh, T. K., Lai, M. J., Chan, L., Tu, Y. K., Banerjee, S., Hu, C. J., & Liou, J. P. (2020). Protective effects of 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates on vascular cognitive impairment. European Journal of Medicinal Chemistry, 187, Article 111915. https://doi.org/10.1016/j.ejmech.2019.111915

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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.",

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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

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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.

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

Abstract

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