Antischistosomal action of thioxo-imidazolidine compounds: an ultrastructural and cytotoxicity study.

Schistosomiasis is a disease caused by helminthes of the genus Schistosoma, which threatens approximately 207 million people worldwide. Recently, strains of Schistosoma mansoni appear to be developing tolerance and resistance against Praziquantel, the most commonly available drug on the market used in the treatment of disease. This worrisome development justifies studies that seek alternatives for the prevention, treatment and cure of this disease. This study aimed to evaluate the in vitro activity of new imidazolidine compounds 1-benzyl-4-[(4-chloro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-5) and 1-(4-chloro-benzyl)-4-[(4-fluoro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-11) against adult worms of S. mansoni. LPSF/PT-5 and LPSF/PT-11 imidazolidine derivatives showed relevant schistosomicidal activity in vitro and induced significant ultrastructural alterations in worms and cell death: results similar to praziquantel. Thus, it is possible that these imidazolidine derivatives can be future candidates as schistosomotic drugs, but further studies are needed to elucidate the induced mechanisms behind this response.

New imidazolidinic bioisosters: potential candidates for antischistosomal drugs.

The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 microM which killed 100% of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.