Cobalt() 8-hydroxyquinoline complexes: structure, cytotoxicity and action mechanism

• Published in: MedChemComm 2016-01, Vol.7 (5), p.86-812
• Main Authors: Zhang, Hai-Rong, Huang, Ke-Bin, Chen, Zhen-Feng, Liu, Yan-Cheng, Liu, You-Nian, Meng, Ting, Qin, Qi-Pin, Zou, Bi-Qun, Liang, Hong
• Format: Article
• Language: English
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c6md00073h

Three cobalt( ii ) complexes, [Co(NOQ) 2 (C 5 H 5 N) 2 ]C 2 H 5 OH ( 1 ), [Co(BrQ) 2 (C 5 H 5 N) 2 ] ( 2 ) and [Co(NQ) 2 (C 5 H 5 N) 2 ] ( 3 ) (NOQ = 5-nitro-8-hydroxyquinoline, BrQ = 5-bromo-8-hydroxyquinoline, NHQ = 2-amino-8-hydroxyquinoline), were synthesized and characterized. Their in vitro cytotoxicity against T-24, BEL-7404, HepG2, HeLa, MGC-803, SKOV-3, HL-7702 and WI-38 cell lines was evaluated. Complexes 1-3 exhibited the highest proliferation inhibition activity against the T-24 tumor cell line with IC 50 values in the range between 7.00 and 16.70 μM. They also displayed selectivity towards T-24 tumor cell lines compared to the normal liver cell line HL-7702 and human fetal lung fibroblast WI-38 cell line. The action mechanism of complex 1 was investigated. It caused apoptotic death of the T-24 cells via G1 cell cycle arrest. Further investigation revealed that complex 1 induced overproduction of reactive oxygen species, which led to mitochondrion-mediated apoptosis. DNA binding studies suggested that intercalation might be the most probable binding mode of the Co( ii ) complexes with ct-DNA. Three cobalt( ii ) complexes with 8-hydroxyquinoline derivatives as ligands were synthesized. They exhibited strong proliferation inhibition activity against T-24 cancer cells, which induced cancer cell apoptosis via intrinsic caspase-mitochondria pathways.