Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species

Abstract

BackgroundSchistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms.MethodsIn this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy.Results5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in hepatopancreas tissues, including degeneration of the endoplasmic reticulum and vacuolization in mitochondria. In addition, transcriptional levels of superoxide dismutase (SOD), acid phosphatase (ACP) and NOS in the hepatopancreas were significantly downregulated as shown by real-time quantitative polymerase chain reaction (RT-PCR). These results indicated that the hepatopancreas is a primary target organ of salicylanilidate.ConclusionsSalicylanilidate not only had deleterious effects on Biomphalaria species and S. mansoni cercariae but also showed very low toxicity to D. rerio, suggesting that it has broad potential applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2313-3) contains supplementary material, which is available to authorized users.

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

“… a Values are given as means with 95% confidence intervals in parentheses b Pearson chi-square goodness-of-fit test c [ 31 ] d [ 34 ] …”

Synthesis, Molluscicidaland Antimicrobial Potentialities of Iron Triad Mononuclear Metal Complexes Incorporating Tridentate Asymmetrical Schiff Base Ligands Containing Soft Sulfur Coordinating Atom

“…The obtained Schiff base ligands and their corresponding metal complexes were tested for their molluscicidal activity according to the standard reported methods, as cited in the literature [14,26,27]. The solutions of the compounds used for the bioassay were prepared with concentrations ranging from (50 ppm, 100 ppm, 500 ppm, 1000 ppm, and 5000 ppm) in DMSO solvent.…”

“…Molluscicidal activity evaluation of the tested compounds was performed by observing the toxicity and lethal dose (LD 50 ) according to the WHO guidelines using the immersion technique and using niclosamide as a control measure [27].…”

“…Some of the obtained ligands and their corresponding metal complexes were tested for their molluscicidal activity against the land snail B. arabica. The toxicity and LD 50 were determined for the tested compounds according to the WHO guidelines using the immersion technique and using niclosamide as a positive control [27]. The number of mortalities and 50% death (LD 50 ) values are shown in Table 3.…”

A New Method to Test Molluscicides against the Philippine Schistosomiasis Snail Vectors

“…ere is a growing interest in phytochemicals with potent molluscicidal activity a er the successful use of Phytolacca dodecandra in the snail population control of schistosome vectors in Egypt [7,8,11]. Synthesis of new compounds and structure-activity relationship with known molluscicides are also gaining popularity [9,10,12,13]. Both research strategies will require an assay which uses a small amount of test substance while maintaining accuracy and reproducibility.…”