Synthesis and cytotoxicity of novel pyrido[1,2-e]purines on multidrug resistant human MCF7 cells.

ABSTRACT

The anticancer activity of 4-methylaminopyridol[1,2-e]purine 6a, 4-(piperidin-1-yl)pyrido[1,2-e]purine 7a and their 7-methyl derivatives 6b, 7b was investigated against the human MCF7 cancer cell line in vitro. The sensitive cell line showed a range of sensitivities to 6a, 6b, 7a, 7b (IC50 1.6 to 7.2 x 10(-4) M) and sensitivity to doxorubicin (IC50 7.5 x 10(-7) M). A resistant cell line with the multidrug resistant phenotype was sensitive to these derivatives (IC50 1.8 to 6.7 x 10(-4) M), doxorubicin (IC50 5 x 10(-5) M) and drug activity seems to be not affected by MDR resistance. Our data show that 6a, 6b, 7a and 7b appear to exert a low cytotoxicity on sensitive and MDR resistant MCF7 human cancer cell lines.