Imidazo [4,5f][1,10] phenanthroline derivatives as inhibitor of c-myc gene expression in A549 cells via NF-kappa B pathway

1,10-Phenanthroline has been shown to exhibit anticancer activity. Here, a series of imidazo [4,5f][1,10] phenanthroline derivatives 1-10 were synthesized and their biological activities were further elucidated. We found that 2-(4-Brominephenyl)-imidazo [4,5f][1,10] phenanthroline (compound 3) possessed potent antiproliferation activities again a variety of tumor cell lines using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometric analysis revealed that compound 3 induced both through apoptosis and necrosis in human lung adenocarcinoma cell line, A549. Moreover, compound 3 treatment led to up-regulation of I kappa B alpha and down-regulation of p65 and c-myc in A549 cells. Taken together, these results suggested that compound 3 inhibited cell proliferation by suppression of NF-kappa B activity and down-regulation of c-myc gene expression and may be a candidate for further evaluation as a chemopreventive and chemotherapeutic agent for human cancers, especially for lung cancer. (C) 2011 Elsevier Ltd. All rights reserved.