RESUMEN
Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50 percent of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.
Asunto(s)
Animales , Antiprotozoarios/farmacología , Tiazoles/farmacología , Tiosemicarbazonas/farmacología , Toxoplasma/efectos de los fármacos , Antiprotozoarios/química , Chlorocebus aethiops , Interacciones Huésped-Parásitos , Microscopía Electrónica de Transmisión , Pruebas de Sensibilidad Parasitaria , Tiazoles/química , Tiosemicarbazonas/química , Toxoplasma/ultraestructura , Células Vero/parasitologíaRESUMEN
Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.
Asunto(s)
Antiprotozoarios/farmacología , Tiazoles/farmacología , Tiosemicarbazonas/farmacología , Toxoplasma/efectos de los fármacos , Animales , Antiprotozoarios/química , Chlorocebus aethiops , Interacciones Huésped-Parásitos , Microscopía Electrónica de Transmisión , Pruebas de Sensibilidad Parasitaria , Tiazoles/química , Tiosemicarbazonas/química , Toxoplasma/ultraestructura , Células Vero/parasitologíaRESUMEN
A new set of derivative thioxothiazolidinones and thioxoimidazolidinones 3,5-dissubstituted has been synthesized with satisfactory yield from the condensation Knoevenagel type between benzaldéhydes and 4-thioxothiazolidin-2-one, 2-thioxothiazolidin-4-one and 1-méthyl-2-thioxoimidazolidin-4-one compounds following by N-alkylation with aryl or acyl halides. The physico-chemical properties of the 5-benzylidene-3-[2-(4-chlorophenyl)-2-oxoethyl]-2 (or 4)-thioxothiazolidin-4 (or 2)-ones and 5-benzylidene-1-methyl-2-thioxoimidazolidin-4-ones synthesized have been described.
Asunto(s)
Imidazoles/química , Tiazoles/química , Tionas/química , Alquilación , Fenómenos Químicos , Química Física , Imidazoles/síntesis química , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Tiazoles/síntesis química , Tionas/síntesis químicaRESUMEN
The synthesis of five chlorobenzyl benzylidene imidazolidinediones and four fluorobenzyl benzylidene thiazolidinediones is described. In order to investigate their antimicrobial activity they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus, Mycobacterium smegmatis and Escherichia coli.
Asunto(s)
Antiinfecciosos/síntesis química , Compuestos de Bencilideno/síntesis química , Imidazoles/síntesis química , Tiazoles/síntesis química , Antibacterianos , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Compuestos de Bencilo/síntesis química , Compuestos de Bencilo/farmacología , Compuestos de Bencilideno/farmacología , Hongos/efectos de los fármacos , Imidazoles/farmacología , Pruebas de Sensibilidad Microbiana , Tiazoles/farmacologíaRESUMEN
The synthesis of six benzylidene thiazolidine-diones and three benzylidene imidazolidine-diones is described. In order to investigate their antimicrobial activity, they are evaluated against micro-organism such as Staphylococcus aureus, Streptococcus feacalis, Mycobacterium smegmatis and Neurospora crassa.
Asunto(s)
Antiinfecciosos/síntesis química , Compuestos de Bencilideno/síntesis química , Hidantoínas/síntesis química , Tiazoles/síntesis química , Antibacterianos , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Compuestos de Bencilideno/farmacología , Hongos/efectos de los fármacos , Hidantoínas/farmacología , Pruebas de Sensibilidad Microbiana , Tiazoles/farmacologíaRESUMEN
The synthesis of six benzylidene thiazolidinediones and four benzylidene imidazolidinediones is described. In order to investigate their antifungal activity, they are evaluated against microorganism such as Candida albicans, Neurospora crassa, Staphylococcus aureus and Escherichia coli.