SÃntese e avaliaÃÃo de atividades Anti-Toxoplama gondii e antimicrobiana de Tiossemicarbazidas, 4-Tiazolidinonas e 1,3,4-TiadiazÃis obidos a partir do Ãster 5-Metil-1H-Imidazol-4-Carboxilato de Etila

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Toxoplasmosis is an infection caused by Toxoplasma gondii, a protozoan parasite with very complex biology and wide distribution in several geographical areas of the globe. In 2005, our research group published a paper reporting an exceptional anti-T. gondii activity for thiosemicarbazones and arylhydrazono-4-thiazolidinones, with a nitro group in aryl moiety. In the recent literature, several works report imidazo-compounds as new potentials antiprotozoal agents. Specially for megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,2,3- thiadiazole) and its analogues as trypanocidal agents. With the aim of to product new actives molecules against T. gondii, we decided to realize the synthesis and in vitro evaluation for acylthiosemicarbazides (and its derivatives: 4-thiazolidinones and 1,3,4-thiadiazoles) obtained from ethyl(5-methyl-1-Himidazole-4-carboxylate) ester. The acylthiosemicarbazides were synthesized by addition reactions between 5-methyl-1-H-imidazole-4-carbohydrazide and substituted isothiocyanates. From acilthiosemicarbazides were obtained two new series: 4-thiazolidinones, by thia-Michael reaction, where maleic anhydride acted as Michael acceptor; and 1,3,4-thiadiazoles by cycledehydration with sulphuric acid. The final products were purified by recrystallizations (acylthiosemicarbazides) and column chromatography (4-thiazolidinones) from appropriate solvents, giving yield ranging between 10% and 94%. All synthesized compounds were characterized by conventional spectroscopic analysis (NMR 1H, NMR 13C and IR) and high resolution mass spectrometry (MS-HR). The formation of acilthiosemicarbazides was confirmed in NMR 13C, where peaks resonated at 181.1-181.0 ppm and 163.1-162.5 ppm assigned for C=S and C=O moieties, respectively. For 4-thiazolidinones, absorption bands around 1397-1378 cm-1, associated with NCS moiety bending vibration, confirmed the ring closure. The 1,3,4-thadiazoles derivatives were characterized by the absence of signals at 181,1-181,0 ppm and 163.1-162.5 ppm in NMR 13C spectroscopy, assigned for C=S and C=O moieties. The existence of chemical shifts in the acilthiosemicarbazides obteined, involving movable hydrogen atoms, was proved by EXSY spectroscopic analysis. The in vitro evaluation of the anti-T. gondii activities showed acilthiosemicarbazides and 1,3,4-thiadiazoles derivatives as the most actives compounds against host vero infected cells and intracellular parasites. These results indicated an application of these compounds as provable anti-T. gondii agents in the future. Finally, the antimicrobial activities evaluation showed weak activities for all tested compounds, against fungal and bacterial strains

ASSUNTO(S)

toxoplasma gondii atividade antimicrobiana 4-tiazolidinona 1,3,4-thiadiazole imidazol 1,3,4-tiadiazol 4-thiazolidinone antimicrobial activity toxoplasma gondii farmacia imidazole

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