Syntheses, crystal structures of copper (II)-based complexes of sulfonamide derivatives and their anticancer effects through the synergistic effect of anti-angiogenesis, anti-inflammation, pro-apoptosis and cuproptosis

Eur J Med Chem. 2024 Dec 15:280:116954. doi: 10.1016/j.ejmech.2024.116954. Epub 2024 Oct 10.

Abstract

Three novel copper(II)-based complexes Cu-1, Cu-2, and Cu-3 containing sulfamethoxazole or sulfamethazine ligand were obtained, and their single structures were characterized. Both Cu-1 and Cu-3 show a broad spectrum of cytotoxicity than Cu-2, and Cu-1 is more cytotoxic than Cu-3. What's interesting is that Cu-1 can exhibit obvious inhibitory effect on the growth of human triple-negative breast cancer in vivo and vitro through anti-proliferative, anti-angiogenic, anti-inflammatory, pro-apoptotic and cuproptotic synergistic effects. Though Cu-3 shows no significant cytotoxicity against MDA-MB-231 cells, it can significantly inhibit the growth of SKOV3 cells in vitro by down-regulating the expression of some key proteins in the VEGF/VEGFR2 signaling pathway and the expression of some pro-inflammatory cytokines, and by disrupting the balance of intracellular reactive oxygen species levels.

Keywords: Anti-Inflammation; Anti-Tumor angiogenesis; Copper (II)-Based complexes; Cuproptosis; Sulfonamide derivatives.

MeSH terms

  • Angiogenesis Inhibitors* / chemical synthesis
  • Angiogenesis Inhibitors* / chemistry
  • Angiogenesis Inhibitors* / pharmacology
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Copper* / chemistry
  • Copper* / pharmacology
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship
  • Sulfonamides* / chemical synthesis
  • Sulfonamides* / chemistry
  • Sulfonamides* / pharmacology

Substances

  • Copper
  • Antineoplastic Agents
  • Sulfonamides
  • Angiogenesis Inhibitors
  • Coordination Complexes
  • Reactive Oxygen Species
  • Anti-Inflammatory Agents