Abstract text

Introduction:

Schistosomiasis is a parasitic disease which causes more than 200 000 human deaths per year and about 200 million infections. The Schistosomiasis was declaimed as a neglected tropical disease (NTD) by the WHO. The only therapeutic option that is used against the infection is Praziquantel.

Due to that, the hazard of emerging resistance against Praziquantel is growing. A reduced sensitivity of the parasites against Praziquantel has already been observed. Therefore, the development of new anti-schistosomal agents is essential.

Objectives:

A Novel class of anti-schistososomal agents should be developed. The in-vitro activity of the substances should be in 10 mM range. In addition, parasites" physiology and morphology should be impacted, while the compounds should not display cytotoxicity against human cell lines at significantly higher concentrations.

Material & Methods:

Structural variations of several moieties of the biarylalkyl carboxylic acid scaffold were carried out through the synthesis of different derivates of the basic scaffold. Compounds were tested against cultured adult Schistosoma mansoni couples and in case of significant activity also against two human cell lines.

Results:

More than 240 compounds with biarylalkyl carboxylic acid moiety were synthesized and tested. The most effective compounds showed anti-schistosomal activity at 10 mM. Furthermore, damaging phenotypes were observed while the agents showed no significant cytotoxicity against human cell lines.

Conclusion:

Using a ligand-based approach to drug design a novel class of anti-schistosomal agents was obtained.

Acknowledgments:

This project was funded by the LOEWE centre DRUID within the Hessian Excellence Initiative and DFG SCHL383-GR1549.

References:

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