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Improving the bioactivity of Zn(II)-curcumin based complexes.

Daniela Pucci1, Alessandra Crispini, Bárbara Sanz Mendiguchía

  • 1Centro di Eccellenza CEMIF.CAL-LASCAMM, CR-INSTM Unità della Calabria, Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci Cubo 14C, Italy. d.pucci@unical.it

Dalton Transactions (Cambridge, England : 2003)
|May 18, 2013
PubMed
Summary

New zinc(II)-curcumin complexes show potent antitumor activity against neuroblastoma cells. Specifically, complexes 1 and 4 exhibit strong cytotoxic effects, inducing apoptosis and inhibiting cell growth, offering promising therapeutic potential.

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Thermochemical Studies of Ni(II) and Zn(II) Ternary Complexes Using Ion Mobility-Mass Spectrometry
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Thermochemical Studies of Ni(II) and Zn(II) Ternary Complexes Using Ion Mobility-Mass Spectrometry

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Area of Science:

  • Coordination Chemistry
  • Medicinal Chemistry
  • Cancer Research

Background:

  • The precursor complex [(bpy-9)Zn(curc)Cl] (A) showed potential as an intercalating antitumor agent.
  • Structural modifications were explored to enhance the bioactivity and introduce new functionalities like electrostatic and covalent interactions.
  • Heteroleptic zinc(II)-curcumin complexes offer a versatile platform for developing novel anticancer agents.

Purpose of the Study:

  • To synthesize and characterize novel Zn(II)-curcumin based heteroleptic complexes (1-5).
  • To evaluate the in vitro antitumor activity of these new complexes against the human neuroblastoma cell line SH-SY5Y.
  • To compare the efficacy of the novel complexes with the precursor complex A.

Main Methods:

  • Synthesis and full characterization of five new Zn(II)-curcumin heteroleptic complexes.
  • In vitro cytotoxic activity testing using a biohybrid membrane system against SH-SY5Y cells.
  • Apoptosis assays including Annexin V and PI staining, JNK, caspase 3 activation, and mitochondrial membrane potential (MMP) changes.

Main Results:

  • All synthesized complexes (1-5) demonstrated strong cytotoxic activity against SH-SY5Y neuroblastoma cells.
  • Complex 1 (ionic tetrafluoroborate) and complex 4 (phenanthroline-based) exhibited the most potent growth inhibition, surpassing the precursor complex A.
  • Complexes 1 and 4 induced a dose-dependent anti-proliferative effect, triggering apoptosis via JNK and caspase 3 activation and MMP changes.

Conclusions:

  • Novel Zn(II)-curcumin heteroleptic complexes possess significant in vitro antitumor potential.
  • Complexes 1 and 4 are particularly effective, demonstrating superior efficacy compared to the precursor.
  • Complex 1 effectively induces caspase-3 activation, highlighting its role in triggering the execution phase of apoptosis.