Designing Trifluoromethyl Pyrazolones for Selective Molluscicidal Activity Against : Toward Sustainable Land Snail Control

TL;DR

This paper introduces new trifluoromethyl pyrazolone compounds that effectively kill land snails while being safer than traditional pesticides.

Contribution

The study presents novel 5-trifluoromethyl-phenylpyrazolone derivatives with potent molluscicidal activity and a dual mode of action.

Findings

Compound 16 showed the highest lethal activity against snails with an LC50 of 0.58 mg/mL.

Treated snails exhibited liver enzyme increases and reduced carbohydrates and lipids.

Histopathological analysis revealed significant cellular damage in snails treated with the compounds.

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 (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- 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 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 GABAA-glutamate chloride ion channel (GluCl) antagonism. Homology modeling
using the 3RHW ( (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.

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