Síntese de protótipos quinoidais heterocíclicos voltados à quimioterapia da Doença de Chagas e ao combate de tumores malignos
AUTOR(ES)
Eufrânio Nunes da Silva Júnior
DATA DE PUBLICAÇÃO
2009
RESUMO
Several 3-arylamino and 3-alkoxy derivatives of nor-β-lapachone and β-lapachone-based 1,2,3-triazoles were synthesized and found to show very potent cytotoxicity against four neoplastic cancer cells: SF-295 (central nervous system), HCT-8 (colon), MDAMB-435 (breast) and HL-60 (leukaemia), with IC50 below 1 μg/mL. Their cytotoxicities were compared to doxorubicin and with their synthetic precursors, β-lapachone and nor-β-lapachone. The activity against normal peripheral blood mononucluear cells (PBMC) showed that some of the compounds were selective against cancer cells. 3-arylamino and 3-alkoxy derivatives of nor-β-lapachone and β-lapachone-based 1,2,3-triazoles were assayed against the infective bloodstream trypomastigote form of Trypanosoma cruzi, the etiological agent of Chagas disease. All the derivatives were more active than the original quinones and some compounds were more active than benznidazole, used as positive control. Several substances described herein emerge as interesting new lead compounds in drug development for Chagas disease and for cancer. Studies towards the obtention of new heterocycles and the complete elucidation of the Hooker peroxide by NMR spectroscopy and X-ray diffraction were accomplished.
ASSUNTO(S)
naftoquinonas quimica doença de chagas naphthoquinones cancer chagas disease câncer
