trichostatin-a and Dementia--Vascular

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.

Topics: Animals; Azepines; Cell Line, Tumor; Clomipramine; Cognitive Dysfunction; Dementia, Vascular; Dose-Response Relationship, Drug; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Protective Agents; Structure-Activity Relationship