The strong in vitro and vivo cytotoxicity of three new cobalt(II) complexes with 8-methoxyquinoline

Three new cobalt(II) complexes, [Co(MQL)(2)Cl-2] (CoCl), (Co(MQL)(2)Br-2] (CoBr), and [Co(MQL)(2)l(2)] (Col), bearing 8-methoxyquinoline (MOO have been designed for the first time. MTT assays showed that CoCl, CoBr, and Col exhibit much better antiproliferative activities than cisplatin toward cisplatin-resistant SK-OV-3/DDP and SK-OV-3 ovarian cancer cells, with IC50 values of as low as 0.32-5.49 mu M. Further, CoCl and Col can regulate autophagy-related proteins in SK-OV-3/DDP cells and, therefore, they can induce primarily autophagy-mediated cell apoptosis in the following order: CoCl > Col. The different antiproliferative activities of the MQL complexes CoCl, CoBr, and Col could be correlated with the lengths of their Co-X bonds, which adopted the following order: Col > CoBr > CoCl. The 8-HOMO complexes CoCl (ca. 60.1%) and Col (ca. 48.8%) also showed potent in vivo anticancer effects after 15 days of treatment. In summary, the MQL ligand highly enhances the antiproliferative activities of cobalt(II) complexes in comparison to other previously reported 8-hydroxyquinoline metal complexes.