Trifluoromethyl ketone-based inhibitors of apoptosis in cerebellar granule neurons.
A variety of aromatic trifluoromethyl ketone derivatives has been studied as inhibitors of apoptosis in cerebellar granule neurons (CGNs). Among them, alpha-trifluoromethyl diketone (2) and benzyl trifluoromethyl ketone (11) were found to be apoptosis inhibitors which can prevent a neurodegenerative disease. Compounds 2 and 11 showed neuroprotection effect on low K+-induced apoptosis in CGNs. Furthermore, these compounds effectively suppressed DNA fragmentation accompanied with apoptosis. The neuroprotection mode of 2 and 11 was not related to inhibition of caspase-3.
Kawase
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan. kawasema@josai.ac.jp
Sunaga
K
K
Tani
S
S
Niwa
M
M
Uematsu
T
T
D000089:Acetic Anhydrides; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005463:Fluoroacetates; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D008333:Mandelic Acids / Q000737:chemistry / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010648:Phenylacetates / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014269:Trifluoroacetic Acid / Q000737:chemistry / Q000494:pharmacology*
D000089:Acetic Anhydrides; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005463:Fluoroacetates; D007659:Ketones; D008333:Mandelic Acids; D018696:Neuroprotective Agents; D010648:Phenylacetates; C017958:trifluoroacetic anhydride; D014269:Trifluoroacetic Acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C025136:phenylacetic acid; C037938:mandelic acid