Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

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.

Síntese e atividade biológica de novas tiossemicarbazonas / Synthesis and biological activity of new thiosemicarbazones

Este trabalho descreve a síntese e avaliaçäo estrutural de nove tiossemicarbazonas, obtidas pela condensaçäo de ariltioacetaldeídos e artiopropanonas substituídas com cloridrato de tiossemicarbazida. Estes novos compostos foram testados in vitro pelo fitoteste Lepidium sativum. Todos eles apresentaram atividade inibidora do crescimento celular (pI50) superior àquela de 5-fluoruacila, composto anticancerígeno, utilizado como referência.

New antimicrobial quinazolinone derivatives

A series of quinazolin-4-ones incorporated with pyridones, iminopyridines, thiazole, semicarbazone and thiosemicarbazone moieties were synthesized. Some tested compounds showed considerable biological activity against some microorganisms

Conductance of cobalt [II] complexes of acetonethiosemi-carbazone chloride and bromide in methanol-water mixtures at 25

The conductance of cobalt [II] complexes of acetone thiosemicarbazone chloride and bromide is measured in methanol-water mixtures covering a dielectric constant ranging between 32.63 - 69.94 at 25C. The data are analyzed using the Fuoss-Onsager equation on an IBM-PC computer. It was found that a degree for chloride increase with the decrease of dielectric constant, while a degree for bromide decreases with the decrease of dielectric constant until a certain value, and then increases thereafter. The plot of log KA vs. 1/D is found to be nonlinear. Finally, the solvent separated-ion pair model is applied to these systems