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S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent-Its Action on the Development of Ascaris suum Eggs In Vitro.

ABSTRACT: Ascaris suum is a soil-transmitted parasite causing ascariasis in pigs, largely limiting livestock production globally. Searching for new drugs affecting all stages of nematode development is necessary and widely postulated. The in vitro activity of S-methyl-(2-methoxycarbonylamino-benzoimidasole-5) thiosulfonate on A. suum developing eggs was studied. Five concentrations of the drug were used-0.625, 1.25, 2.5, 5 and 10 mM during 24, 48 and 72 h of exposure. After drug treatment, the eggs were washed and cultured in 0.05 M HCl at 27 °C for 20 days. Both the concentration and duration of the drug exposure had an inhibitory impact on the percentage of L2 larvae developed. The best effect was obtained after 72 h of incubation in 5 mM drug solution, only 1.9 ± 3.3% of the larvae developed to the L2 stage. Moreover, no SNP was detected at codon 167, which is correlated with benzimidazole resistance, in the tested samples. For the first time, it has been demonstrated that S-M-(2-MKA-BZ-5)TS seems to be a potential ovicidal anti-helminthic agent. It may lead to the elimination of parasites and reduce environmental contamination from roundworm eggs. The ovicidal effects of the drug should be additionally confirmed by further infection studies using experimental animals.

SUBMITTER: Dmitryjuk M

PROVIDER: S-EPMC7690733 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent-Its Action on the Development of Ascaris suum Eggs In Vitro.

Dmitryjuk Małgorzata M Szczotko Magdalena M Kubiak Katarzyna K Trojanowicz Radosław R Parashchyn Zhanna Z Khomitska Halyna H Lubenets Vira V

Pharmaceuticals (Basel, Switzerland) 20201023 11

Ascaris suum is a soil-transmitted parasite causing ascariasis in pigs, largely limiting livestock production globally. Searching for new drugs affecting all stages of nematode development is necessary and widely postulated. The in vitro activity of S-methyl-(2-methoxycarbonylamino-benzoimidasole-5) thiosulfonate on A. suum developing eggs was studied. Five concentrations of the drug were used-0.625, 1.25, 2.5, 5 and 10 mM during 24, 48 and 72 h of exposure. After drug treat ...[more]

PMID: 33113959

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Project description:BackgroundThe treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently high. This high drug pressure may result in the development of BZ resistance in STHs and so there is an urgent need for surveillance systems detecting molecular markers associated with BZ resistance. A critical prerequisite to develop such systems is an understanding of the gene family encoding β-tubulin proteins, the principal targets of BZ drugs.Methodology and principal findingsFirst, the β-tubulin gene families of Ascaris lumbricoides and Ascaris suum were characterized through the analysis of published genomes. Second, RNA-seq and RT-PCR analyses on cDNA were applied to determine the transcription profiles of the different gene family members. The results revealed that Ascaris species have at least seven different β-tubulin genes of which two are highly expressed during the entire lifecycle. Third, deep amplicon sequencing was performed on these two genes in more than 200 adult A. lumbricoides (Ethiopia and Tanzania) and A. suum (Belgium) worms, to investigate the intra- and inter-species genetic diversity and the presence of single nucleotide polymorphisms (SNPs) that are associated with BZ resistance in other helminth species; F167Y (TTC>TAC or TTT>TAT), E198A (GAA>GCA or GAG>GCG), E198L (GAA>TTA) and F200Y (TTC>TAC or TTT>TAT). These particular SNPs were absent in the two investigated genes in all three Ascaris populations.SignificanceThis study demonstrated the presence of at least seven β-tubulin genes in Ascaris worms. A new nomenclature was proposed and prioritization of genes for future BZ resistance research was discussed. This is the first comprehensive description of the β-tubulin gene family in Ascaris and provides a framework to investigate the prevalence and potential role of β-tubulin sequence polymorphisms in BZ resistance in a more systematic manner than previously possible.

Dataset Information

S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent-Its Action on the Development of Ascaris suum Eggs In Vitro.

Publications

<i>S</i>-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent-Its Action on the Development of <i>Ascaris suum</i> Eggs In Vitro.

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