Eighteen 5,7-Dihalo-8-quinolinol and 2,2′-Bipyridine Co(II) Complexes as a New Class of Promising Anticancer Agents

Here we first report the design of a series of bis-chelate Co­(II) 5,7-dihalo-8-quinolinol-phenanthroline derivative complexes, [Co­(py)­(QL1)2] (Co1), [Co­(py)­(QL2)2] (Co2), [Co­(Phen)­(QL1)2] (Co3), [Co­(Phen)­(QL2)2] (Co4), [Co­(DPQ)­(QL1)2]·(CH3OH)4 (Co5), [Co­(DPQ)­(QL2)2] (Co6), [Co­(DPPZ)­(QL1)2]·CH3OH (Co7), [Co­(MDP)­(QL1)2]·3H2O (Co8), [Co­(ODP)­(QL1)2]·CH3OH (Co9), [Co­(PPT)­(QL1)2]·CH3OH (Co10), [Co­(ClPT)­(QL1)2] (Co11), [Co­(dpy)­(QL3)2] (Co12), [Co­(mpy)­(QL1)2] (Co13), [Co­(Phen)­(QL4)2] (Co14), [Co­(ODP)­(QL4)2] (Co15), [Co­(mpy)­(QL4)2]I (Co16), [Co­(ClPT)­(QL4)2] (Co17), and [Co­(ClPT)­(QL5)2] (Co18), with 5,7-dihalo-8-quinolinol and 2,2′-bipyridine mixed ligands. The antitumor activity of Co1Co18 has been evaluated against human HeLa (cervical) cancer cells in vitro (IC50 values = 0.8 nM–11.88 μM), as well as in vivo against HeLa xenograft tumor growth (TIR = 43.7%, p < 0.05). Importantly, Co7 exhibited high safety in vivo and was more effective in inhibiting HeLa tumor xenograft growth (43.7%) than cisplatin (35.2%) under the same conditions (2.0 mg/kg). In contrast, the H-QL1 and DPPZ ligands greatly enhanced the activity and selectivity of Co7 in comparison to Co1Co6, Co8Co18, and previously reported cobalt­(II) compounds. In addition, Co7 (0.8 nM) inhibited telomerase activity, caused G2/M phase arrest, and induced mitochondrial dysfunction at a concentration 5662.5 times lower than Co1 (4.53 μM) in related assays. Taken together, Co7 showed low toxicity, and the combination could be a novel Co­(II) antitumor compound candidate.