Donor-Acceptor-Donor Strategy Rouses the Photodynamic Therapy Anticancer Activity of a Bis-terpyridyl Ru(II) Complex

J Med Chem. 2024 Aug 8;67(15):13435-13445. doi: 10.1021/acs.jmedchem.4c01307. Epub 2024 Jul 30.

Abstract

Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Coordination Complexes* / chemical synthesis
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Photochemotherapy*
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / chemistry
  • Photosensitizing Agents* / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Ruthenium* / chemistry
  • Ruthenium* / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Ruthenium
  • Photosensitizing Agents
  • Coordination Complexes
  • Pyridines