In vitro activity, ultrastructural analysis and in silico pharmacokinetic properties (ADMET) of thiazole compounds against adult worms of Schistosoma mansoni

The present work aimed to carry out in vitro biological assays of thiazole compounds against adult worms of Schistosoma mansoni, as well as the in silico determination of pharmacokinetic parameters to predict the oral bioavailability of these compounds. In addition to presenting moderate to low cytotoxicity against mammalian cells, thiazole compounds are not considered hemolytic. All compounds were initially tested at concentrations ranging from 200 to 6.25 & mu;M against adult worms of S. mansoni parasites. The results showed the best activity of PBT2 and PBT5 at a concentration of 200 & mu;M, which caused 100% mortality after 3 h of incubation. While at 6 h of exposure, 100% mortality was observed at the concentration of 100 & mu;M. Subsequent studies with these same compounds allowed classifying PBT5, PBT2, PBT6 and PBT3 compounds, which were considered active and PBT1 and PBT4 compounds, which were considered inactive. In the ultrastructural analysis the compounds PBT2 and PBT5 (200 & mu;M) promoted integumentary changes with exposure of the muscles, formation of integumentary blisters, integuments with abnormal morphology and destruction of tubercles and spicules. Therefore, the compounds PBT2 and PBT5 are promising antiparasitics against S. mansoni.

Automated summary

The aim of this study was to conduct in vitro biological assays and pharmacokinetic parameter determination of thiazole compounds against adult worms of Schistosoma mansoni. Thiazole compounds showed moderate to low cytotoxicity against mammalian cells and were not hemolytic. PBT2 and PBT5 exhibited the highest activity against the parasites, causing 100% mortality after 3 hours of incubation at a concentration of 200μM. Ultrastructural analysis revealed that PBT2 and PBT5 induced changes in the integument, including exposure of muscles, formation of blisters, abnormal morphology, and destruction of tubercles and spicules. Thus, PBT2 and PBT5 are promising antiparasitic agents against S. mansoni.