Schistosomiasis, also known as snail fever and bilharzia, is a chronic parasitic disease caused by trematode flatworms of the genus Schistosoma. The disease affects hundreds of millions of individuals worldwide and it ranks among the most prominent neglected diseases due to the lack of interest from pharmaceutical companies. In the absence of a vaccine, currently treatments rely on a single agent, praziquantel, which does not prevent reinfection and the emergence of drug resistance is a concern. The potential loss of the only effective available schistosomicidal drug underscores the need of new/alternative treatments. Using in vitro whole-organism screens of S. mansoni, we evaluated the anti-schistosomal activity of several representatives from a compound collection of tubulin/microtubule-interacting molecules, including the natural products, paclitaxel, vinblastine, colchicine and epothilones, as well as non-naturally occurring small molecules. The screening and selection of compounds, which was based on both qualitative and quantitative assessments of anti-schistosomal activity led to the prioritization of a series of phenylpyrimidines (Figure 1) with promising parasiticidal activity against both schistosomula and adult worms. The design, synthesis and evaluation of a series of phenylpyrimidines congeners leading to a characterization of the structure anti-schistosomal activity relationship will be presented.

Structure-activity relationships of phenypyrimidine compounds as novel candidate treatments for schistosomiasis

2019 Fall National Meeting

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