Therapeutic potential of hydantoin and thiohydantoin compounds against Schistosoma mansoni: An integrated in vitro, DNA, ultrastructural, and ADMET in silico approach

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 μM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 μM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 μM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni. [Display omitted] •Hydantoin and thiohydantoin compounds have shown in vitro anti-parasitic activity against Schistosoma mansoni.•Thiohydantoin SC04 caused 100 % mortality at 50 µM after 24 hours, likely by inhibiting motor activity.•The compounds are predicted to have good pharmacokinetic profiles and oral availability in in silico models.•They exhibited low cytotoxicity on mammalian cells in vitro.•Thiohydantoin SC04 caused significant damage to the worms' integument, with blistering and erosion.