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• W2970546836 abstract "Abstract The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against Schistosoma mansoni couples in vitro. Further optimisation of the compounds led to an increase in anti‐schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure–activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against S. mansoni at 25 μ m . The best five compounds showed an anti‐schistosomal activity up to 10 μ m and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100 μ m . These compounds are promising candidates for further optimisation toward the new anti‐schistosomal agents." @default.
• W2970546836 created "2019-09-05" @default.
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• W2970546836 date "2019-09-18" @default.
• W2970546836 modified "2023-09-26" @default.
• W2970546836 title "Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti‐schistosomal Activity" @default.
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• W2970546836 doi "https://doi.org/10.1002/cmdc.201900423" @default.
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