High antitumor activity of 5,7-dihalo-8-quinolinolato cerium complexes

• DOI: 10.1016/j.ejmech.2013.08.007
• Publication Date: 2013-08-13T22:47:07Z
• Authors: Zhen-Feng Chen; Jian-Hua Wei; Yan-Cheng Liu; Mei Liu; Yun-Qiong Gu; Ke-Bin Huang; Meng Wang; Hong Liang
• Keywords: 0303 health sciences; Binding Sites; Molecular Structure; Cell Cycle; Antineoplastic Agents; Apoptosis; Cerium; 3. Good health; Inhibitory Concentration 50; 03 medical and health sciences; Halogens; Coordination Complexes; Cell Line, Tumor; Quinolines; Humans; Cisplatin; Drug Screening Assays, Antitumor; Cell Proliferation

Three cerium complexes: [Ce(ClQ)4] (1) (H-ClQ=5,7-dichloro-8-hydroxylquinoline), [Ce(ClIQ)4]·CH2Cl2·0.5H2O (2) (H-ClIQ=5-chloro-7-iodo-8-hydroxylquinoline) and [Ce2(BrQ)4(H-BrQ)(H2O)3Cl2]·1.5H2O (3) (H-BrQ=5,7-dibromo-8-hydroxylquinoline) were synthesized. The structures of 1 and 2 are mononuclear whereas 3 has a binuclear structure. Compared with the H-ClQ, H-ClIQ and H-BrQ, complexes 1-3 exhibited significantly higher cytotoxicity (IC50=0.09-5.23 μM) to SK-OV-3 and BEL-7404, 1 and 2 exhibited higher cytotoxicity to NCI-H460. Most the complexes and ligands exhibited higher cytotoxicity than cisplatin. Complexes 1-3 are much more sensitive to SK-OV-3 than to human normal liver cell HL-7702. Their antitumor activities were achieved through cell apoptosis and arrest at G0/G1-phase. Studies on the binding properties of 1-3 to DNA indicate that intercalation is the most probable binding mode.