TY - JOUR
T1 - Synthesis and biological evaluation of pyrethroid insecticide-derivatives as a chemical inducer for Bdnf mRNA expression in neurons
AU - Matsuya, Yuji
AU - Ihara, Daisuke
AU - Fukuchi, Mamoru
AU - Honma, Daisuke
AU - Itoh, Kiyoshi
AU - Tabuchi, Akiko
AU - Nemoto, Hideo
AU - Tsuda, Masaaki
N1 - Funding Information:
This study was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (Project Number 20390023, M.T.), and the Mitsubishi Foundation (M.T.).
PY - 2012/4/15
Y1 - 2012/4/15
N2 - Brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal synaptic plasticity. A decrease of plasticity in the brain may be related to the pathogenesis of neurodegenerative or psychiatric disorders. Pyrethroid insecticides, which affect sodium channels in neurons, are widely used to control insect pests in agriculture and in the home. We previously found that deltamethrin (DM), a type II pyrethroid, increased Bdnf mRNA expression in cultured rat cortical neurons. However, the cyano group at the α-position of type II pyrethroids is likely susceptible to hydrolytic degradation and, its degraded product, hydrogen cyanide, could generate a cellular toxicity in the human body. To determine if the cyano group is required for the Bdnf exon IV-IX (Bdnf eIV-IX) mRNA expression induced by type II pyrethroids, for this study we synthesized a series of derivatives, in which the cyano group at the α-position was replaced with an ethynyl group. Then we added various substituents at the terminal position of the ethynyl group, and biologically evaluated the effects of these derivatives on Bdnf eIV-IX mRNA expression. These ethynyl derivatives induced the Bdnf eIV-IX mRNA expression in a concentration-dependent manner, at varying levels but lower levels than that evoked by DM. The mechanisms for the Bdnf induction and the morphological changes of neurons were the same whether the cyano or ethynyl group was included in the compounds.
AB - Brain-derived neurotrophic factor (BDNF) plays a fundamental role in neuronal synaptic plasticity. A decrease of plasticity in the brain may be related to the pathogenesis of neurodegenerative or psychiatric disorders. Pyrethroid insecticides, which affect sodium channels in neurons, are widely used to control insect pests in agriculture and in the home. We previously found that deltamethrin (DM), a type II pyrethroid, increased Bdnf mRNA expression in cultured rat cortical neurons. However, the cyano group at the α-position of type II pyrethroids is likely susceptible to hydrolytic degradation and, its degraded product, hydrogen cyanide, could generate a cellular toxicity in the human body. To determine if the cyano group is required for the Bdnf exon IV-IX (Bdnf eIV-IX) mRNA expression induced by type II pyrethroids, for this study we synthesized a series of derivatives, in which the cyano group at the α-position was replaced with an ethynyl group. Then we added various substituents at the terminal position of the ethynyl group, and biologically evaluated the effects of these derivatives on Bdnf eIV-IX mRNA expression. These ethynyl derivatives induced the Bdnf eIV-IX mRNA expression in a concentration-dependent manner, at varying levels but lower levels than that evoked by DM. The mechanisms for the Bdnf induction and the morphological changes of neurons were the same whether the cyano or ethynyl group was included in the compounds.
KW - BDNF
KW - Deltamethrin
KW - Ethynyl substituent
KW - Pyrethroid
KW - Structure-activity relationship
UR - http://www.scopus.com/inward/record.url?scp=84859431793&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2012.02.048
DO - 10.1016/j.bmc.2012.02.048
M3 - 学術論文
C2 - 22429507
AN - SCOPUS:84859431793
SN - 0968-0896
VL - 20
SP - 2564
EP - 2571
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 8
ER -