当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl)-3-isothiazolols.

Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl)-3-isothiazolols.

Abstract：

:γ-Aminobutyric acid (GABA) receptors are important targets of parasiticides/insecticides. Several 4-substituted analogs of the partial GABAA receptor agonist 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL) were synthesized and examined for their antagonism of insect GABA receptors expressed in Drosophila S2 cells or Xenopus oocytes. Thio-4-PIOL showed weak antagonism of three insect GABA receptors. The antagonistic activity of Thio-4-PIOL was enhanced by introducing bicyclic aromatic substituents into the 4-position of the isothiazole ring. The 2-naphthyl and the 3-biphenylyl analogs displayed antagonist potencies with half maximal inhibitory concentrations in the low micromolar range. The 2-naphthyl analog induced a parallel rightward shift of the GABA concentration-response curve, suggesting competitive antagonism by these analogs. Both compounds exhibited weak insecticidal activities against houseflies. Thus, the orthosteric site of insect GABA receptors might be a potential target site of insecticides.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Liu G,Furuta K,Nakajima H,Ozoe F,Ozoe Y

doi

10.1016/j.bmc.2014.07.021

subject

Has Abstract

pub_date

2014-09-01 00:00:00

pages

4637-45

issue

17

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00537-9

journal_volume

22

pub_type

杂志文章

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