Discovery of the pyridylphenylureas as novel molluscicides against the invasive snail Biomphalaria straminea, intermediate host of Schistosoma mansoni

The snail Biomphalaria straminea is one of the intermediate hosts of Schistosoma mansoni. Biomphalaria straminea is also an invasive species, known for its strong capability on peripheral expansion, long-distance dispersal and colonization. Using molluscicides to control snail populations is an important strategy to interrupt schistosomiasis transmission and to prevent the spread of the invasive species. In this study, a series of pyridylphenylurea derivatives were synthesized as potential molluscicides. Their impact on adult snails and egg masses was evaluated. Acute toxicity to fish of the derivatives was also examined to assess their effect on non-target organisms. The preliminary mechanisms of action of the derivatives were studied by enzyme activity assays. The representative compounds, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (compound 8) and 1-(4-bromophenyl)-3-(pyridin-3-yl)urea (compound 9), exhibited strong molluscicidal activity against adult snails with LD50 values of 0.50 and 0.51 mg/l and potent inhibitory effects on snail egg hatchability with IC50 values of 0.05 and 0.09 mg/l. Notably, both compounds showed good target specificity with potent molluscicidal capability observed in snails, but very low toxicity to local fishes. Furthermore, the exposure of compounds 8 and 9 significantly elevated the enzyme activities of acid phosphatase and nitric oxide synthase of the snails, while no significant change was recorded in the activities of alkaline phosphatase, acetylcholine esterase and superoxide dismutase. The results suggested that compounds 8 and 9 of pyridylphenylurea derivatives could be developed as promising molluscicide candidates for snail control.