RESUMO
Mitotane is a chiral drug used to treat adrenocortical carcinoma, being metabolized to the o,p'-dichlorodiphenyl acetic acid (o,p'-DDA), also a chiral compound. Despite of its therapeutic significance, the overall ratios and enantiomers have not been known. In this study, we analyzed the enantiomers of mitotane and o,p'-DDA in the plasma of patients by a newly developed chiral-phase method employed in two-dimensional chromatography. Important differences were observed in the ratio of (S)/(R)-mitotane, which varied substantially from 1:1.2 to 1:10 whereas the (S)/(R)-o,p'-DDA ratio was relatively conserved, at approximately 2:1. These findings provide evidence for the enantioselective metabolism and provide a method for further analyses of mitotane and metabolites, which can explain the variation in the therapeutic response.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Mitotano/uso terapêutico , Mitotano/metabolismo , Carcinoma Adrenocortical/tratamento farmacológico , Estereoisomerismo , Cromatografia Líquida de Alta Pressão/métodos , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/metabolismoRESUMO
Two new hydronaphthoquinones, aggregatins E and F (1 and 2, resp.) were isolated from the tubers of Sinningia aggregata (Ker-Gawl.) Wiehler (Gesneriaceae), along with twelve known compounds aggregatin D (3), tectoquinone (4), 1-hydroxy-2-methylanthraquinone (5), icosyl ferulate (6), pustuline (7), 1,6-dihydroxy-2-methylanthranquinone (8), 6-hydroxy-2-methylanthraquinone (9), 7-hydroxy-2-methylanthraquinone (10), tyrosol (11), halleridone (12), calceolarioside B (13), and cornoside (14). All compounds were identified by analysis of spectroscopic and spectrometric data. Compounds 3, 4, and 10 had already been reported in this species. Compounds 2 and 3 were evaluated against several tumor cell lines, but only 3 exhibited activities against UACC-62, 786-0 and OVCAR-3 cell lines, with IC50 values of 12.3, 12.8 and 0.3â µg/ml, respectively, without toxic effects on non-cancer cell line HaCat (human keratinocyte).