ml9b00356_si_002.pdf (2.6 MB)
Eighteen 5,7-Dihalo-8-quinolinol and 2,2′-Bipyridine Co(II) Complexes as a New Class of Promising Anticancer Agents
journal contribution
posted on 2019-11-09, 13:03 authored by Ting Meng, Qi-Pin Qin, Hua-Hong Zou, Kai Wang, Fu-Pei LiangHere
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 Co1–Co18 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 Co1–Co6, Co8–Co18, 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.