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DOI: https://doi.org/10.6023/A26080293

Article

Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex

  • Zhou Hongyu ,
  • Luo Fuliu ,
  • Liu Minshan ,
  • Tan Mingxiong ,
  • Zhou Zhen ,
  • Liang Hong ,
  • Qin Qipin
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  • aGuangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, Yulin 537000;
    bSchool of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004
†These authors contributed equally to this work.

Received date: 2026-08-19

  Online published: 2026-09-17

Supported by

Natural Science Foundation of Guangxi (nos. 2026GXNSFHA00640357, 2026GXNSFHA00640014 and 2025GXNSFAA069961), the National Natural Science Foundation (no. 22267020), the Bagui Youth top-notch personnel program of Guangxi (no. 2024ZKBGQB01) and the China University Students Innovative Project(nos. 202510606147, X2026106060034 and X2026106060148).

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Abstract

To enhance the anti-cancer efficacy of metal-based drugs, two cobalt(II) complex, [Co(QL’)(phen)(CH3OH)Cl]·(CH3OH) (QLCo1) and [Co(QL’)2(CH3OH)2] (QLCo2), were synthesized via coordination of 6,7-dichloro-5,8-quinolinone (QL) and 1,10-phenanthroline (phen) with CoCl2·6H₂O under controlled conditions. The structures of QL, QLCo1 and QLCo2 were determined by nuclear magnetic resonance (NMR), elemental analysis (ELA), ultraviolet-visible absorption spectroscopy (UV-Vis), infrared spectroscopy (IRS) and mass spectrometry (ESI-MS). In the complexes QLCo1 and QLCo2, the central cobalt(II) atom exhibits a six-coordinated octahedral structure. Additionally, compared with cisplatin (Cis-Pt) and QLCo2, the anti-cancer activity and potential mechanism of the phen-modified cobalt(II) complex QLCo1 were investigated. Compared with normal liver cells (HL-7702, AML12), human cervical cancer cells (HeLa), and human lung cancer cells (A549), QLCo1 exhibited better inhibitory effects on human lung cancer cisplatin-resistant cells (A549/CDDP), with an IC50 value of 0.30±0.02 μmol/L; this potency was markedly superior to Cis-Pt (67.2 ± 1.3 μmol/L), QL (>100.0 μmol/L), CoCl2·6H₂O(>100.0 μmol/L), phen (>100.0 μmol/L) and QLCo2 (IC50= 4.0±0.8 μmol/L), respectively. Flow cytometry, Western blotting experiments, cell uptake and immunofluorescence experiments revealed showed that QLCo1 and QLCo2 induced apoptosis in A549/CDDP cells, with apoptosis rates of 46.45% and 44.17%, respectively. Complexes QLCo1 and QLCo2 mediated endogenous apoptosis in A549/CDDP cancer cells through the mitophagy pathway, indicating that phen enhanced the ability of the cobalt(II) complex QLCo2 to induce apoptosis in A549/CDDP cancer cells. From the cobalt uptake assay, complex QLCo1 exhibited obvious priority on the cell uptake effect than QLCo2, which should should be undoubtedly correlated with the key roles of the phen ligand of QLCo1. Moreover, QLCo1 could significantly inhibit the growth of A549/CDDP solid tumors, with an inhibition rate of 50.6%, which was markedly higher than that of Cis-Pt (ca. 26.6%). In conclusion, this study has identified a 6,7-dichloro-5,8-quinolinone dithiocarbamate complex, named QLCo1, which can effectively induce apoptosis in A549/CDDP cancer cells through mitochondrial autophagy.

Key words： Cobalt(II) complex; 6,7-dichloro-5,8-quinolinedione; mitophagy

Cite this article

Zhou Hongyu , Luo Fuliu , Liu Minshan , Tan Mingxiong , Zhou Zhen , Liang Hong , Qin Qipin . Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex[J]. Acta Chimica Sinica, 0 : 0 . DOI: 10.6023/A26080293

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