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

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 were characterized based on H NMR, C-APT and F- NMR spectra as well as mass spectroscopy. Compounds , , and demonstrated potent anti- activities, with exhibiting the highest lethal activity (LC = 0.58 mg/mL), surpassing the current standard, methomyl (LC = 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 , , , and at the LC 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 . Additionally, typical CNS toxicity symptoms, including paralysis and excessive fluid secretion, suggest a dual mode of action: gastrointestinal toxicity and GABA-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 GABA 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.