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Pd(II)/diphosphine/curcumin complexes as potential anticancer agents.

Jocely L Dutra1,2, João Honorato3, Angélica Graminha1

  • 1Departamento de Química, Universidade Federal de São Carlos - UFSCar, CP 676, CEP 13561-901, São Carlos, SP, Brazil. jocely.dut@hotmail.com.

Dalton Transactions (Cambridge, England : 2003)
|June 28, 2024
PubMed
Summary
This summary is machine-generated.

New palladium(II) complexes with curcumin show potent anticancer activity against various cancer cell lines. Complex A1 demonstrated significant cytotoxicity, inducing apoptosis and ROS production in cisplatin-resistant ovarian cancer cells.

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Area of Science:

  • Inorganic Chemistry
  • Medicinal Chemistry
  • Cancer Research

Background:

  • Palladium(II) complexes are investigated for their selective in vitro cytotoxicity against cancer cells.
  • Curcumin, a natural product, possesses anticancer properties and is explored as a ligand in metal complexes.
  • Combining palladium(II) with phosphine ligands and curcumin aims to develop novel anticancer agents.

Purpose of the Study:

  • To synthesize and characterize a series of novel palladium(II)-curcumin-phosphine complexes.
  • To evaluate the in vitro anticancer activity of these complexes against various human tumor and non-tumor cell lines.
  • To investigate the mechanism of action of the most potent complex in cisplatin-resistant ovarian cancer cells.

Main Methods:

  • Synthesis of five palladium(II) complexes: [Pd(cur)(PPh3)2]PF6 (A1) to [Pd(cur)(dppf)]PF6 (A5).
  • Characterization using elemental analysis, spectroscopy (NMR, UV-Vis, IR), and X-ray crystallography for selected complexes.
  • In vitro cytotoxicity evaluation using the MTT assay against MDA-MB-231, SK-BR-3, A549, MRC-5, A2780, and A2780cis cell lines.

Main Results:

  • All synthesized complexes (A1-A5) exhibited significant in vitro anticancer activities against tested tumor cell lines.
  • Complexes generally showed lower IC50 values (higher potency) compared to free curcumin and palladium precursors.
  • Complex A1 displayed superior cytotoxicity, particularly against MDA-MB-231 and ovarian cancer cell lines (A2780, A2780cis), outperforming cisplatin.
  • Complex A1 induced apoptosis and cell cycle arrest in A2780cis cells and potent ROS generation.

Conclusions:

  • The synthesized palladium(II)-curcumin complexes represent promising anticancer agents with enhanced activity over free curcumin.
  • Complex A1 is a potent candidate for further investigation, especially for overcoming cisplatin resistance in ovarian cancer.
  • The mechanism involves ROS induction, apoptosis, and cell cycle arrest, highlighting its therapeutic potential.