Antiproliferative Activity of Novel Derivative of Thiopyran on Breast and Colon Cancer Lines and DNA Binding

摘要

Dimethyl-5-acetyl-4-methyl-6-(4-methylphenylimino)-6H-thiopyran-2,3-dica rboxylate (4) has been synthesized and its antiproliferative activity is reported here. Compound 4 inhibited the growth of human colon cancer cell line HCT-15 with an IC(50) value of 3.5 mu M and of breast cancer cell line MCF-7 with an IC(50) value of 1.5 mu M in a dose/time-dependent manner using a sulforhodamine B assay. Moreover, suppression of clonogenic activity occurred after exposure to 4 at a concentration of 4 mu M for HCT-15 and 1.7 mu M for MCF-7. The results also showed tumor cell invasion through matrigel and cell adhesion. The effect of ligand complexation on DNA structure led to overall affinity constant of K(4-DNA) = 9.8 x 10(4) M(-1).