M A Maaroof Hend, AlNeyadi Shaikha S, Raouf Yasir S, I El-Akhrasy Fatma, Hassan Abdalla E A, A I Abouelkhair Reham
Applied Nucleic Acids Research Center & Chemistry Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt.
Plant Protection Research Institute, Agricultural Research Center, Dokki, Giza 12622, Egypt.
J Agric Food Chem. 2025 Aug 13;73(32):19907-19920. doi: 10.1021/acs.jafc.4c12327. Epub 2025 Jun 11.
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.
陆生腹足纲动物是重要的农业害虫和疾病传播者，给农作物及各个农业领域带来重大挑战。合成农药仍然是害虫防治的主要方法，但害虫抗药性的增强以及对非目标物种的有害影响凸显了对新型、更安全替代品的迫切需求。在此，我们报告了一系列5-三氟甲基-苯基吡唑啉酮作为潜在杀螺剂对（O. F. 米勒，1774）蜗牛的合成及评估。新合成的5-三氟甲基-苯基吡唑啉酮衍生物通过¹H NMR、¹³C-APT和¹⁹F-NMR光谱以及质谱进行了表征。化合物1、3、5和7表现出强大的杀螺活性，其中化合物7表现出最高的致死活性（LC₅₀ = 0.58 mg/mL），超过了目前的标准药剂灭多威（LC₅₀ = 2.28 mg/mL）。在用化合物1、3、5和7以LC₅₀值处理蜗牛后，观察到肝转氨酶（AST和ALT）、乙酰胆碱酯酶（AChE）显著增加，同时总碳水化合物和脂质减少。对处理过的蜗牛消化腺的组织病理学分析显示细胞受到损伤，其中化合物7导致的结构细胞完整性丧失和功能损害最为严重。此外，典型的中枢神经系统毒性症状，包括麻痹和过多的液体分泌，表明其具有双重作用模式：胃肠道毒性和GABA - 谷氨酸氯离子通道（GluCl）拮抗作用。使用3RHW（（莫帕斯，1900））模板和GluCl ζ亚基序列进行同源建模，以生成用于虚拟筛选的3RHW - ζ嵌合体。此外，使用GABA GluCl结构进行诱导契合对接（IFD）研究，以生成与三氟甲基苯基吡唑兼容的结合口袋。从这些模型得出的对接分数支持了观察到的杀螺活性。这些发现确定了强效的4-取代-5-三氟甲基苯基吡唑啉酮作为更安全、有效的杀螺剂的潜在有用候选物。
