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

Journal of the Brazilian Chemical Society

Eufrânio N. Da Silva Júnior²  Maria Aline B. F. De Moura¹  Antonio V. Pinto¹  Maria Do Carmo F. R. Pinto¹  Maria Cecília B. V. De Souza²  Ana J. Araújo¹  Claudia Pessoa¹  Letícia V. Costa-lotufo¹  Raquel C. Montenegro¹  Manoel Odorico De Moraes¹  Vitor F. Ferreira²  Marilia O. F. Goulart² 

[1] ,Universidade Federal Fluminense Instituto de Química Departamento de Química OrgânicaNiterói RJ ,Brazil

关键词: lapachones;    cytotoxicity;    reduction potentials;    clog P;    naphthoquinone-triazoles;    trypanocidal agents;   

DOI  :  10.1590/S0103-50532009000400007

来源: SciELO

【 摘 要 】

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).

【 授权许可】

CC BY   
 All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License