Abstract
The present study was undertaken to identify noncompetitive γ-aminobutyric acid receptor (GABAR) antagonists that are effective in nematodes, as well as to examine the hypothesis that the noncompetitive antagonism of the GABAR underlies the nematocidal activity of quassinoids against free-living nematodes of the Diplogastridae family. First, 14 known GABAR antagonists were screened for the effectiveness of their nematocidal activity in Diplogastridae. As a result, 3-isopropyl-1-phospha-2,6,7-trioxabicyclo[2.2.2]octane 1-sulfides (3-isopropyl-BPTs) were found to have high nematocidal activities, and 4-cyclohexyl-3-isopropyl-BPT ( 23) and 3-isopropyl-4-(2-propenyl)-BPT ( 27) were the two most potent analogues; these compounds are equipotent to samaderine B and more potent than the anthelmintic abamectin. 23-resistant nematodes, selected by challenge with 23, showed cross-resistance to samaderine B. 23 (10 μM) reduced [ 3H] 23 binding to nematode membranes by 30.4%. Samaderine B (10 μM) resulted in a similar level of the inhibition, but had neither additive nor synergistic effects on the 23 inhibition of [ 3H] 23 binding. These findings suggest that samaderine B shares a common binding site with the GABAR antagonist 23 in Diplogastridae. The results of comparative molecular field analysis, a method of three-dimensional quantitative structure–activity relationship analysis, supported this conclusion.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
