Platinum(II) compounds of tetracyclines as potential anticancer agents: cytotoxicity, uptake and interactions with DNA

Journal of the Brazilian Chemical Society

Priscila P. Silva²  Flávia C. S. De Paula²  Wendell Guerra²  Josianne N. Silveira¹  Françoise V. Botelho¹  Leda Q. Vieira¹  Tiago Bortolotto¹  Franciele L. Fischer¹  Giselle Bussi¹  Hernán Terenzi¹  Elene C. Pereira-maia² 

[1] ,Universidade Federal de Santa Catarina Campus Reitor João David Ferreira Lima Departamento de QuímicaFlorianópolis SC ,Brazil

关键词: platinum(II) compounds;    cytotoxicity;    cellular uptake;    DNA binding;   

DOI  :  10.1590/S0103-50532010000700011

来源: SciELO

【 摘 要 】

The antitumoral properties of PtII compounds and the favorable characteristics of tetracyclines led us to study PtII compounds of tetracycline (tc) and doxycycline (dox) as candidates for anticancer agents. [PtCl2(dox)], 1, is more potent than [PtCl2(tc)], 2, in inhibiting the growth of chronic myelogenous leukemia cells. Compounds 1 and 2 form a ternary complex with DNA withK values of 3.85×10(4) and 5.43×10(4), respectively. The compounds displace ethidium bromide from DNA sites, which points to an intercalative mechanism. Both complexes decrease DNA eletrophoretic mobility and melting temperature. After incubation of cells with 1 and 2, the DNA was extracted and the adducts formed were quantified. At the concentration that the compounds are cytotoxic to cancer cells, they do not affect macrophages viability. The rate of uptake of the doxycycline complex in cells is three times higher than that of the tetracycline complex and this seems to be determinant for its higher activity.

【 授权许可】

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