New 5-Aryl-Substituted 2-Aminobenzamide-Type HDAC Inhibitors with a Diketopiperazine Group and Their Ameliorating Effects on Ischemia-Induced Neuronal Cell Death
| Autor: | Chi-Jing Choong, Hideaki Kanki, Genki Kubo, Masahiko Taniguchi, Ayana Hotei, Kumiko Nishiyama, Hideki Mochizuki, Yoshiyuki Hirata, Shinichi Uesato, Tsutomu Sasaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Programmed cell death Ischemia lcsh:Medicine Diketopiperazines Pharmacology Models Biological Neuroprotection Article Brain Ischemia Cell Line Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound medicine Animals Humans Structure–activity relationship lcsh:Science Neurons Multidisciplinary Cell Death Molecular Structure Chemistry lcsh:R medicine.disease HDAC1 Rats XIAP Histone Deacetylase Inhibitors Neuroprotective Agents 030104 developmental biology Cell culture Benzamides lcsh:Q Methyl group |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-19664-9 |
| Popis: | We previously synthesized new 5-thienyl-substituted 2-aminobenzamide-type HDAC1, 2 inhibitors with the (4-ethyl-2,3-dioxopiperazine-1-carboxamido) methyl group. K-560 (1a) protected against neuronal cell death in a Parkinson’s disease model by up-regulating the expression of XIAP. This finding prompted us to design new K-560-related compounds. We examined the structure activity relationship (SAR) for the neuronal protective effects of newly synthesized and known K-560 derivatives after cerebral ischemia. Among them, K-856 (8), containing the (4-methyl-2,5-dioxopiperazin-1-yl) methyl group, exhibited a promising neuronal survival activity. The SAR study strongly suggested that the attachment of a monocyclic 2,3- or 2,5-diketopiperazine group to the 2-amino-5-aryl (but not 2-nitro-5-aryl) scaffold is necessary for K-560-related compounds to exert a potent neuroprotective effect. |
| Databáze: | OpenAIRE |
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