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

Journal of the Brazilian Chemical Society

Bortolotto, Tiago¹  Pereira-Maia, Elene C.¹  Botelho, Françoise V.¹  Silva, Priscila P.¹  Bussi, Giselle¹  Universidade Federal de Santa Catarina, Florianópolis, Brazil¹  Guerra, Wendell¹  Terenzi, Hernán¹  Universidade Federal de Minas Gerais, Belo Horizonte, Brazil¹  Paula, Flávia C. S. de¹  Fischer, Franciele L.¹  Vieira, Leda Q.¹  Silveira, Josianne N.¹ 

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

DOI  :  10.1590/S0103-50532010000700011

学科分类：化学（综合）

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 3.85×104 and 5.43×104, 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】

Unknown