Cytotoxic, trypanocidal activities and physicochemical parameters of nor-²-lapachone-based 1,2,3-triazoles

• Autor(a) principal: Silva Júnior,Eufrânio N. da
• Data de Publicação: 2009
• Outros Autores: Moura,Maria Aline B. F. de, Pinto,Antonio V., Pinto,Maria do Carmo F. R., Souza,Maria Cecília B. V. de, Araújo,Ana J., Pessoa,Claudia, Costa-Lotufo,Letícia V., Montenegro,Raquel C., Moraes,Manoel Odorico de, Ferreira,Vitor F., Goulart,Marilia O. F.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009000400007
• topic: lapachones; cytotoxicity; reduction potentials; clog P; naphthoquinone-triazoles; trypanocidal agents

The cytotoxicities of five nor-²-lapachone-based 1,2,3-triazoles and the precursor azidonaphthoquinone were assayed against six neoplasic cancer cell lines: SF-295 (central nervous system), HCT-8 (colon), MDAMB-435 (melanoma), HL-60 (leukaemia), PC-3 (prostate) and B-16 (murine melanoma). IC50 values ranging from 0.43 to 9.48 µM were obtained. 3-(4-(1-hydroxycyclohexyl)-1H-1,2,3-triazol-1yl)-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione proved highly cytotoxic to MDAMB-435, with IC50 even lower than the one from doxorubicin (positive control). In an attempt to correlate physicochemical parameters (reduction potentials and calculated log P) with cytotoxic activity, electrochemical studies were conducted in acetate buffer, pH 4.5, using a vitreous carbon electrode and calculated log P values were obtained. Despite the absence of a structural conjugative interaction between the two systems (quinone and triazole), the heterocyclic group was found to influence the voltammetric behaviour, as indicated by anodic shifts in the reduction potentials. No correlation was found between EpIc and cytotoxicity. In contrast, a comparison of EpIc with previously reported trypanocidal activities reconfirmed the trend for higher activity coupled with better quinone electrophilicity (> EpIc).A leading term in the correlation of cytoxicity, despite the absence of a linear correlation, was the calculated log P: the lower the lipophilicity, the lower the cytoxicity (> IC50).