Chalcone-based synthesis of a new Pyrazoline derivative: Molecular docking and anthelmintic evaluation against Schistosoma mansoni.

Chalcones and their derivatives have attracted considerable interest in drug discovery due to literature reports describing their diverse biological activities. In this study, we evaluated the in vitro schistosomicidal activity of a chalcone derivative and its corresponding pyrazoline derivative against adult Schistosoma mansoni worms. The chalcone (1a) and its newly synthesized pyrazoline derivative (1b), reported here for the first time, showed generally favorable predicted pharmacokinetic and ADMET profiles. Both compounds were predicted to exhibit high gastrointestinal absorption (GIA), suitable blood-brain barrier (BBB) permeability, and full compliance with Lipinski's rule of five. Molecular docking analyses predicted favorable interactions of both molecules with Cathepsin B, Thioredoxin Glutathione Reductase (TGR), and β-tubulin, biologically relevant proteins in S. mansoni, with docking scores and interaction profiles supporting plausible ligand-target recognition. Complementary in vitro assays further supported the schistosomicidal activity of 1a and 1b through phenotypic analysis, revealing marked effects on parasite viability and morphology. Notably, both compounds induced 100.0% mortality at 20.0 μg mL-1 within 24 h, and even at 5.0 μg mL-1 they reduced parasite motility and caused morphological alterations in both male and female worms. In addition, the compounds affected egg production and release, an important biological parameter associated with immunopathogenesis and maintenance of the S. mansoni life cycle. Overall, the integrated findings support compounds 1a and 1b, particularly the novel pyrazoline derivative 1b, as preliminary structural hits for further optimization and mechanistic investigation.