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A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant

Franziska Bannwart1,2, Leon F Richter3, Simon Stifel3

  • 1Department of Human Medicine, MSH Medical School Hamburg, Am Kaiserkai 1, 20457 Hamburg, Germany.

Journal of Medicinal Chemistry
|August 28, 2024
PubMed

Insights

New gold(I) complexes show anticancer promise. Complex 1 targets cancer cells, induces apoptosis, and overcomes drug resistance, offering potential for novel cancer therapies.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Pharmacology

Background:

  • Metal-organic gold(I) complexes exhibit antiproliferative effects.
  • Existing cancer therapies face challenges with cytostatic resistance.

Purpose of the Study:

  • To synthesize novel gold(I) bis-tetrazolylidene complexes.
  • To evaluate their potential as anticancer agents.
  • To overcome multidrug resistance in cancer cells.

Main Methods:

  • Synthesis of cationic 1,3-disubstituted gold(I) bis-tetrazolylidene complexes.
  • Apoptosis induction assessment via propidium iodide staining and flow cytometry.
  • Evaluation of efficacy in multidrug-resistant cancer cell lines.

Main Results:

  • Gold(I) complex 1 selectively targets malignant cells, inhibiting growth.
  • Complex 1 induces apoptosis without necrosis.
  • It overcomes doxorubicin resistance and sensitizes resistant cells to cytostatic drugs.

Conclusions:

  • Gold(I) complex 1 demonstrates significant therapeutic potential.
  • It likely acts via the mitochondrial pathway, targeting BCL-2 family proteins.
  • This complex offers a promising strategy against drug-resistant cancers.

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