PMID- 22429507
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20191210
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 20
IP  - 8
DP  - 2012 Apr 15
TI  - Synthesis and biological evaluation of pyrethroid insecticide-derivatives as a 
      chemical inducer for Bdnf mRNA expression in neurons.
PG  - 2564-71
LID - 10.1016/j.bmc.2012.02.048 [doi]
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 alpha-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 alpha-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.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Matsuya, Yuji
AU  - Matsuya Y
AD  - Department of Organochemical Design and Synthesis, Graduate School of Medicine 
      and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
FAU - Ihara, Daisuke
AU  - Ihara D
FAU - Fukuchi, Mamoru
AU  - Fukuchi M
FAU - Honma, Daisuke
AU  - Honma D
FAU - Itoh, Kiyoshi
AU  - Itoh K
FAU - Tabuchi, Akiko
AU  - Tabuchi A
FAU - Nemoto, Hideo
AU  - Nemoto H
FAU - Tsuda, Masaaki
AU  - Tsuda M
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120303
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insecticides)
RN  - 0 (Pyrethrins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cerebral Cortex/cytology/drug effects/metabolism
MH  - Insecticides/chemical synthesis/chemistry/*pharmacology
MH  - Molecular Conformation
MH  - Neurons/cytology/*drug effects/metabolism
MH  - Pyrethrins/chemical synthesis/chemistry/*pharmacology
MH  - RNA, Messenger/*drug effects/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Sodium Channels/metabolism
MH  - Structure-Activity Relationship
EDAT- 2012/03/21 06:00
MHDA- 2012/09/05 06:00
CRDT- 2012/03/21 06:00
PHST- 2012/02/08 00:00 [received]
PHST- 2012/02/20 00:00 [revised]
PHST- 2012/02/21 00:00 [accepted]
PHST- 2012/03/21 06:00 [entrez]
PHST- 2012/03/21 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
AID - S0968-0896(12)00150-2 [pii]
AID - 10.1016/j.bmc.2012.02.048 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2012 Apr 15;20(8):2564-71. doi: 10.1016/j.bmc.2012.02.048. Epub 
      2012 Mar 3.