title: Imidazo [4,5f][1,10] phenanthroline derivatives as inhibitor of c-myc gene expression in A549 cells via NF-κB pathway.
abstract: 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 IκBα 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-κB 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.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Sun
authors.forename: Wei-Zhang
authors.initials: WZ
authors.lastname: Wang
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Mao
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Mei
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis; D010618:Phenanthrolines / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D010618:Phenanthrolines; D016271:Proto-Oncogene Proteins c-myc; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C025205:1,10-phenanthroline