The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.

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.

Preparation, characterization, thermal studies, photochemical behaviours and antimicrobial activity of complexes derived from 5-methyl-3-furaldehyde thiosemicarbazone and HG[II] salts of hallo acids

Complexes from of 5-methyl-3-furaldehydethiosemicarbazone [5M3HFTSC] and Hg[II] salts derived from inorganic [HCl] and organic hallo acids [CHCl2COOH or CF3COOH] have been prepared. There chemical structures were characterized using elemental analyses, conductivity spectral measurements, thermogravimetric methods and photochemical behaviours. The thermal studies of such complexes using thermogravimetric analysis [TGA], derivatives thermogravimetry [DrTG] from ambient temperature to 750°C showed three decomposition steps. These studies indicated that the thermal decompositions are not simples. The photolysis of the studied compounds has been carried out in the presence of H2O2. It was found that, the photolysis was enhanced in the presence of H2O2 due to the generation of .OH radicals which are very strong oxidizing agent. Biological activity of theses compounds was tested and screened for their in-vitro antibacterial and antifungal activity. The mixed ligand complexes generally are more active than the binary and free thiosemicarbazne ligand

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.

Estudio de un posible mecanismo de acción antitumoral de tiosemicarbazonas / Study of a possible mechanisms of antitumorous action of thiosemicarbazones

Se estudiaron por espectroscopía UV la tiosemicarbazida (TSC), el 2-amino 5-metil 1,3,4 tiadiazol (MTDZ), la tiosemicarbazona del acetaldehido (AITSC), la tiosemicarbazona del ácido fórmico (FTSC) y los siguientes sistemas: K3 (Fe (CN)6)-AITSC, K3 (Fe (CN)6)-FTSC, Na3 (Co (NO2)6)-AITSC, Na3- (Co(NO2)6)-FTSC, CuCL2 AITSC, CuCL2-FTSC. Estos sistemas tambièn fueron estudiados or cromatografía de capa delgada; se comprobó que la AITSC se exida al MTDZ y se propuso que un posible mecanismo de acción antitumoral sea a través de procesos redox, donde las tiosemicarbazonas se oxiden bajo la acciòn de biometales presentes en el organismo. En el caso de la FTSC no se pudo comprobar la oxidación a su correspondiente tiadiazol, pudiendo explicarse esto a través de que son necesarias condiciones más enérgicas para que ocurra la oxidación