Synthesis, Environmental Residues And Molluscicidal Mechanism Of Novel Spirulina Compounds

Vector control is widely used in the prevention and control of parasitic diseases.Freshwater snails play important roles as the intermediate hosts of many parasites.Among several vector control methods,chemical molluscicides have a fast onset and good effect and is widely used for snail control.Niclosamide is the only commercially available molluscicide recommended by the World Health Organization,but its high toxicity to fish and other non-target organisms which strictly limits its application.Therefore,it is of vital important to develop a new type of molluscicide that has strong molluscicidal effect against freshwater snails and low toxicity to non-target organisms.Our previous study described a novel molluscicide 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea and named as pyridylphenylurea,which exhibits strong molluscicidal effects against different species of snails and has low toxicity to non-target organisms.In this study,pyridylphenylurea was used as the lead compound to derivatize its pyridyl moiety with a variety of aliphatic alkanes and non-aromatic heterocycles.A total of 16compounds were synthesized.¹H-NMR,¹³C-NMR,HRMS were used for characterization.Subsequently,Oncomelania hupensis was used to test the mollusicicdial effect of 16 newly synthesized conpounds.The results indicated that the substitution of pyridyl moiety seriouly reduces the molluscicidal effect of pyridylphenylurea,which provides ideas and experience for the subsequent derivatization.For the registration of pyridylphenylurea as a candidate molluscicide,the final residue test of pyridylphenylurea in soil is completed by liquid chromatography.Twenty-five percentage pyridylphenylurea sulfate wettable powder was applied at a dose of 20000 g a.i./ha for 1-2times,with an interval of 10 days.The final residual concentrations of pyridylphenylurea sulfate are 2.08-6.67 mg/kg in the 50 and 60 days after the last application of pyridylphenylurea,which provides a reference for further use in field.In order to help further development of novel molluscicde,mode of action of pyridylphenylurea against Pomacea canaliculata was explored by TMT-based comparative proteomics.A total of 245 differentially expressed proteins were identified.Functional annotation and enrichment analyses identified GO terms and KEGG pathways involved in de novo purine biosynthesis,ribosome components and translation process were significantly enriched and downregulated.The results indicated that pyridylphenylurea treatment had substantial effects on the synthesis of genetic material,translation process,and protein synthesis of P.canaliculata and were likely the main cause of snail mortality.