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Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (<jats:bold>15\u201331<\/jats:bold>) and three pyrazoles (<jats:bold>32\u201334<\/jats:bold>) were synthesized and evaluated for their antiparasitic properties against ex vivo adult <jats:italic>Schistosoma mansoni<\/jats:italic> worms. Of the 20 compounds tested, six had a 50% effective concentration (EC<jats:sub>50<\/jats:sub>) below 30\u00a0\u03bcM. Our best hit, pyrazoline <jats:bold>22<\/jats:bold>, showed promising activity against adult schistosomes, with an EC<jats:sub>50<\/jats:sub>\u2009&lt;\u200910\u00a0\u00b5M. Additionally, compound <jats:bold>22<\/jats:bold> 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\u2013activity 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\u2019 filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.<\/jats:p>","DOI":"10.1038\/s41598-021-02792-0","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T11:06:05Z","timestamp":1638788765000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Pyrazoline derivatives as promising novel antischistosomal agents"],"prefix":"10.1038","volume":"11","author":[{"given":"Cristiane S.","family":"Morais","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Mengarda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio B.","family":"Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine B.","family":"Enes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius C.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina C.","family":"Esp\u00edrito-Santo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abolghasem","family":"Siyadatpanah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polrat","family":"Wilairatana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara R. 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