Tegumental Changes in Adult Schistosoma mansoni Induced by a New Imidazolidinic Derivative

Abstract

Aims: Verify the potential of the schistosomicidal imidazolidine derivative (5Z)-3-(4-bromo-benzyl)-5-(4-chloro-benzylidene)-4-thioxo-imidazolidin-2-one. Study Design: In this study, we tested the imidazolidinic derivative 3 through in vitro evaluations, cytotoxicity assay and analysis of Scanning Electron Microscopy to verify its therapeutic potential in the treatment of schistosomiasis. Place and Duration of Study: Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Fundação Oswaldo Cruz (FIOCRUZ)/PE and (FIOCRUZ)/BA between January 2013 and march 2014. Methodology: This study was approved by the Ethics Committee on Animal Use Research Center Aggeu Magalhães/Oswaldo Cruz Fundação (CPqAM/FIOCRUZ) authorized by the license No. 21/2011. Male albino Swiss mice were used Mus musculus 25 days old weighing 50 grams. Compound 3 was assayed for its cytotoxicity through cell J774 macrophage lineage. The amount of inhibitory concentration (LC50) was determined by nonlinear regression using the Graph Pad Prism version 5.01. Then the compound was evaluated against adult worms of S. mansoni by performing the activity in vitro at doses 100-20µg/mL and ultrastructural investigation by Scanning Electron Microscopy (SEM) at doses of 100 and 60μg/ml. The PZQ was the positive control of the experiment. Results: The derivative 3 showed LC50 of 29.7±3.9mM. Compound 3 was able to have decreased motility of S. mansoni culminating with a mortality rate of 100% at doses of 60 and 100µg/mL on the fourth day of observation of the experiment. In the SEM, the compound caused various soft tissue changes of S. mansoni parasites such as blistering, destruction of the integument with loss of spines and tubercles, body contraction and windy. Conclusion: The derivative imidazolidine 3 showed a promising schistosomicidal activity in vitro. However, conducting further studies with the completion of work in front of the live schistosomiasis is required.