RESUMO
Praziquantel has been the drug most widely used therapy against different forms of schistosomiasis around the world. However, this treatment has shown ineffective in humans and in experimental models of Schistosoma mansoni. New therapeutic alternatives have been tested, including the imidazolidine derivative LPSF/PT-09, which has shown high therapeutic potential in vitro. In this work, we tested the schistosomal activity of this derivative in doses of 250mg/kg and 200mg/kg in mice experimentally infected with a high parasite load of S. mansoni. Parasitological evaluations related to the number of S. mansoni worms and their oviposition were performed during the acute phase of the disease and have demonstrated moderate effectiveness of 30-54,4%. However, LPSF/PT-09 did not influence oviposition of the parasites or the embryonic development of the eggs. The results obtained in this model showed that the imidazolidine derivative LPSF/PT-09 presented significant antischistosomal activity in vivo, posing as a potential candidate for this class of drugs. However, a better understanding of the pharmacokinetics and pharmacodynamics of the imidazolidine derivative LPSF/PT-09 is needed.
Assuntos
Hidrazonas/farmacologia , Imidazóis/farmacologia , Esquistossomicidas/farmacologia , Tioidantoínas/farmacologia , Animais , Colágeno/metabolismo , Hidrazonas/química , Imidazóis/química , Intestinos/efeitos dos fármacos , Intestinos/parasitologia , Fígado/efeitos dos fármacos , Fígado/parasitologia , Masculino , Camundongos , Óvulo/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomicidas/química , Tioidantoínas/químicaRESUMO
Hydantoins and their derivatives constitute a group of pharmaceutical compounds with anticonvulsant and antiarrhythmic properties, and are also used against diabetes. N-3 and C-5 substituted imidazolidines are examples of such products. As such, we have developed a synthesis of 2,4-dione and 2-thioxo-4-one imidazolidinic derivatives by reaction of amino acids with C-phenylglycine, phenyl isocyanate and phenyl isothiocyanate. Four amino-derivatives IG(1-4) and eight imidazolidinic derivatives, IM(1-8), were obtained in yields of 70-74%. The mass, infrared, (1)H and (13)C-NMR spectra of representative products are discussed.
Assuntos
Glicina/análogos & derivados , Glicina/química , Imidazolidinas/síntese química , Tioidantoínas/síntese química , Imidazolidinas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Tioidantoínas/químicaRESUMO
In the title compound, C(6)H(8)N(2)O(2)S, also known as N-acetyl-2-thiohydantoin-alanine, the molecules are joined by N-H...O hydrogen bonds, forming centrosymmetric R2(2)(8) dimers; these dimers are linked by C-H...O interactions to form R2(2)(10) rings, thus forming C2(2)(10) chains that run along the [101] direction.