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  3. A thiosemicarbazone-based dinuclear copper(II) complex: potent antiproliferative activity, distinct cell-type-specific anticancer mechanisms and robust in vivo antitumor efficacy

A thiosemicarbazone-based dinuclear copper(II) complex: potent antiproliferative activity, distinct cell-type-specific anticancer mechanisms and robust in vivo antitumor efficacy

  • Bioorg Chem. 2026 Sep 5:179:109981. doi: 10.1016/j.bioorg.2026.109981.
Shufang Wu 1,  Qihan Feng 1,  Yan-Bo Wu 1,  Sisi Feng 1,  Zeyu Peng 2,  Caixia Yuan 3,  Xinhua Li 4,  Liping Lu 1,  Lijuan Qiu 5,  Ai Wang 6
Affiliations

Affiliations

  • 1 Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, China.
  • 2 State Key Laboratory of Clean and Efficient Coal Utilization, Taiyuan University of Technology, Taiyuan 030024, Shanxi, China.
  • 3 Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, China. Electronic address: [email protected].
  • 4 Department of Materials and Chemical Engineering, Taiyuan University, Taiyuan 030032, Shanxi, China.
  • 5 Basic Medicine School, Naval Medical University, Shanghai 200433, China. Electronic address: [email protected].
  • 6 Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, Shanxi, China. Electronic address: [email protected].
PMID: 42150409 DOI: 10.1016/j.bioorg.2026.109981
Abstract

A feasible way to avoid chemoresistance in Cancer therapy is to endow a single drug with multiple Anticancer mechanisms. In this work, we propose that a multinuclear metal complex may be a promising drug candidate when its metal centers possess different coordination environments. Our proposal has been demonstrated by our studies on a dinuclear Cu(II) complex [Cu2LCl2(H2O)] (1, H2L = 2,2'-Bis[1-(2-pyrazinyl)ethylidene]carbonothioic dihydrazide), in which the two Cu centers adopt square planar tetracoordination and square pyramidal pentacoordination, respectively. Such a characteristic structure not only induces potent antiproliferative activity against multiple human Cancer cells (IC50 = 0.68-1.94 μM), but also leads to distinct cell-type-specific Anticancer mechanisms: Suppression of Proteasome activity in human colon Cancer HCT-116 cells, but inhibition of protein tyrosine Phosphatase 1B and T-cell protein tyrosine Phosphatase in the human breast Cancer MCF-7 cells. Together with the low toxicity to normal cells and high in vivo antitumor efficacy, 1 represents a promising candidate of the Anticancer metallodrugs for overcoming chemoresistance.

Keywords

Anticancer mechanism; Antiproliferative activity; Copper complex; In vivo antitumor efficacy; Metallodrug; Thiosemicarbazone derivative.

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