SÃntese e AvaliaÃÃo das Atividades Anti-Toxoplasma gondii e Antimicrobiana de BenzaldeÃdo 4-Fenil-3-tiossemicarbazonas e Derivados 2[(Fenilmetileno)hidrazono]-3-fenil-4-tiazolidinona-5-substituÃdos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Parasitic diseases, as toxoplasmosis, affect millions of people, and they are responsible for some of the most important and prevalent diseases of humans and domestic animals. These diseases result in considerable morbidity and mortality worldwide, especially in developing countries. The toxoplasmosis is caused by an intracellular parasite, Toxoplasma gondii, and is associated with severe pathologies, including pneumonia, myocarditis and pulmonary necrosis. In recent works, our research group has reported the synthesis and evaluation of anti-T. gondii activity of thiosemicarbazones and 4-thiazolidinones substituted at arylhydrazone moiety with nitro substituents. This paper was pioneer, because of the inexistence of studies in literature involving the action of these two classes of compounds on intracellular parasite. In order to investigate the anti-T. gondii and antimicrobial activities of new structural analogues, we describe the synthesis, elucidate the structure and in vitro biological activities of new Benzaldehyde 4-phenyl-3-thiosemicarbazones and three series of 2-[(Phenylmethylene)hydrazono]-3-phenyl-4-thiazolidinone-5-substituted, introducing electron-withdrawing or electron-donating substituents at arylhydrazone moiety in both derivatives. The thiosemicarbazones were synthesized by condensation reactions between 4-phenylthiosemicarbazide and substituted benzaldehydes. From thiosemicarbazones were obtained the 4-thiazolidinones, by reactions with maleic anhydride (Michael acceptor), ethyl chloroacetate and ethyl 2-cyano-3[(4-nitro)phenyl]-acetate. All final compounds were purified by recrystallizations, giving yields ranging between 36-100%, and characterized based on their physical, analytical and spectral data (NMR 1H, NMR 13C and IR). These results of antimicrobial activity indicated that some 4-thiazolidinone derivatives with a acethyl substituent at C-5 position of the 4-tiazolidinone ring showed significant activities against M. luteus, M. tuberculosis and Candida sp. (IMUR 4249). All thiossemicarbazone and 4-thiazolidinone derivatives significantly reduced the percentage of infected cells and mean number of tachyzoites per cell in 1 and 2 mM concentration. Various compounds showed best results when compared with hydroxyurea and sulfadiazine. The toxicity of majority compounds was more effective against intracellular parasites, with IC50 values ranging from 0,05 to 1 mM. It can be concluded that thiosemicarbazones and 4-thiazolidinones provide interesting leads for anti-T. gondii drug discovery

ASSUNTO(S)

4-tiazolidinonas atividade antimicrobiana thiosemicarbazone 4-thiazolidinone anti-toxoplasma gondii antimicrobial activity anti-toxoplasma gondii activity tiossemicarbazonas farmacia

ACESSO AO ARTIGO

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