Abstract：
BACKGROUND: Owing to the nonavailability of any clear targets for molluscicides against Pomacea canaliculata, target-based screening strategy cannot be employed. In this study, the molluscicidal effects of typical pesticides on P. canaliculata were evaluated to obtain the molluscicide target. A series of arylpyrrole compounds were synthesized based on the discovered target, and their structure-activity relationships explored. A preliminary strategy for screening molluscicides based on specific targets was also developed.
RESULTS: A laboratory colony of P. canaliculata was developed, which showed no difference in sensitivity to niclosamide compared with the wild group, while exhibiting a higher stability against pesticide response. Mitochondrial adenosine triphosphate (ATP) synthase inhibitors and mitochondrial membrane potential uncouplers were identified and validated as potential targets for molluscicide screening against P. canaliculata. A series of arylpyrrole compounds were designed and synthesized. The median lethal concentration of 4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile (Compound 102) was 10-fold lower than that of niclosamide.
CONCLUSIONS: New molluscicide targets were discovered and validated, and preliminary strategies were explored for pesticide screening based on these targets. Compound 102 exhibited a high molluscicidal activity and had a great potential value for exploring a molluscicide to control P. canaliculata. © 2024 Society of Chemical Industry.
RESULTS: A laboratory colony of P. canaliculata was developed, which showed no difference in sensitivity to niclosamide compared with the wild group, while exhibiting a higher stability against pesticide response. Mitochondrial adenosine triphosphate (ATP) synthase inhibitors and mitochondrial membrane potential uncouplers were identified and validated as potential targets for molluscicide screening against P. canaliculata. A series of arylpyrrole compounds were designed and synthesized. The median lethal concentration of 4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile (Compound 102) was 10-fold lower than that of niclosamide.
CONCLUSIONS: New molluscicide targets were discovered and validated, and preliminary strategies were explored for pesticide screening based on these targets. Compound 102 exhibited a high molluscicidal activity and had a great potential value for exploring a molluscicide to control P. canaliculata. © 2024 Society of Chemical Industry.
摘要：
背景：由于无法获得针对Pomaceacanaliculata的杀软体动物剂的任何明确目标（P.泪小管)，不能采用基于目标的筛查策略。在这项研究中,评价了典型农药对小耳藻的杀软体动物作用，以获得杀软体动物的靶标。基于发现的目标，合成了一系列芳基吡咯化合物，并探讨了构效关系。还开发了基于特定靶标筛选杀软体动物剂的初步策略。
结果：开发了泪珠菌的实验室菌落，与野生组相比，对氯硝柳胺的敏感性没有差异，同时对农药反应表现出更高的稳定性。线粒体三磷酸腺苷(ATP)合成酶抑制剂和线粒体膜电位解偶联剂被鉴定并验证为针对小泪虫的杀软体动物剂筛选的潜在靶标。设计并合成了一系列芳基吡咯化合物。4-溴-2-（4-氯苯基）-5-（三氟甲基）-1H-吡咯-3-甲腈（化合物102）的致死浓度中位数（LC50）比氯硝柳胺低10倍。
结论：发现并验证了新的杀软体动物靶标，并根据这些目标探索了农药筛选的初步策略。化合物102表现出较高的杀软体动物活性,并且对于探索一种杀软体动物剂以控制小泪虫具有很大的潜在价值。本文受版权保护。保留所有权利。
结果：开发了泪珠菌的实验室菌落，与野生组相比，对氯硝柳胺的敏感性没有差异，同时对农药反应表现出更高的稳定性。线粒体三磷酸腺苷(ATP)合成酶抑制剂和线粒体膜电位解偶联剂被鉴定并验证为针对小泪虫的杀软体动物剂筛选的潜在靶标。设计并合成了一系列芳基吡咯化合物。4-溴-2-（4-氯苯基）-5-（三氟甲基）-1H-吡咯-3-甲腈（化合物102）的致死浓度中位数（LC50）比氯硝柳胺低10倍。
结论：发现并验证了新的杀软体动物靶标，并根据这些目标探索了农药筛选的初步策略。化合物102表现出较高的杀软体动物活性,并且对于探索一种杀软体动物剂以控制小泪虫具有很大的潜在价值。本文受版权保护。保留所有权利。
