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Journal of agriculture and Food Chemistry
American Chemical Society
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| Abstract: |
Terrestrial gastropods are significant agricultural pests and disease carriers, posing major challenges to farm crops and
various agricultural domains. Synthetic pesticides remain the primary method of pest control, but rising resistance and harmful
effects on nontarget species highlight the urgent need for new, safer alternatives. Herrin, we report on the synthesis and the
evaluation of a series of 5-trifluoromethyl-phenylpyrazolones against Monacha cartusiana (O. F. Müller, 1774) snails as potential
molluscicidal agents. The newly synthesized 5-trifluoromethyl-phenyl pyrazolones derivatives 11−24 were characterized based on
1H NMR, 13C-APT and 19F- NMR spectra as well as mass spectroscopy. Compounds 11, 16, 17 and 18 demonstrated potent anti-M.
cartusiana activities, with 16 exhibiting the highest lethal activity (LC50 = 0.58 mg/mL), surpassing the current standard, methomyl
(LC50 = 2.28 mg/mL). Significant increase in liver transaminase enzymes (AST and ALT), acetylcholinesterase (AChE), along with
reduction in total carbohydrates and lipids, were observed after the treatment of M. cartusiana snails with compounds 11, 16, 17, and
18 at the LC50 values. Histopathological analysis of the digestive glands of treated snails revealed induced cellular damage, with the
greatest structural cellular integrity loss and functional impairment observed for compound 16. Additionally, typical CNS toxicity
symptoms, including paralysis and excessive fluid secretion, suggest a dual mode of action: gastrointestinal toxicity and GABAAglutamate
chloride ion channel (GluCl) antagonism. Homology modeling using the 3RHW (Caenorhabditis elegans (Maupas, 1900))
template and a GluCl ζ-subunit sequence were used to generate a 3RHW- ζ chimera for virtual screening. Additionally, induced fit
docking (IFD) studies using GABAA GluCl structures were used to generate trifluoromethylphenylpyrazole-compatible binding
pockets. Docking scores derived from these models were found to support the observed molluscicidal activity. These findings
identified potent 4-substituted-5-trifluoromethylphenylpyrazolones as potential useful candidates for safer, effective molluscicides.
KEYWORDS: terrestrial gastropods, land snail control, phenyl-pyrazolone, molluscicidal agents, induced fit docking,
GABAA-GluCl blockers
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