Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC₅₀) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC₅₀ < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.

Polyamines are substances involved in many aspects of cell growth, division, and differentiation. Because of the metabolic differences between host cells and parasite cells, polyamine metabolism has been considered as a potential target for the chemotherapy of parasitic diseases. The aim of this work was to evaluate the schistosomicidal activity of differentN-alkylated diamines (3a–3h), amino alcohols (4a–4d), and glycosylated amino alcohols (10a–10d). Compounds were prepared by synthetic methods and submitted toin vitroevaluation against adult worms ofSchistosoma mansoni. At 100 μM,3b,3e, and3has well as4a,4b,4d,10a,10b, and10dresulted in 100% mortality of adult schistosomes. Compound3d(12.5 to 100 μM) caused the death of 100% of both male and female adult schistosomes, while3f(12.5 to 100 μM) resulted in 100% mortality of only male adult worms, whereas no mortality in female worms was observed. Compounds3dand3fwere also able to reduce viability and decrease production of developed eggs in comparison with the negative control group. Diamines3dand3fmay represent useful lead compounds for further optimization in order to develop new schistosomicidal agents.