Multicationic ruthenium phthalocyanines as photosensitizers for photodynamic inactivation of multiresistant microbes

Ana Belén Domínguez1, Daniel Ziental2, Jolanta Dlugaszewska3

  • 1Departamento de Química Orgánica, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain.

Insights

Multicationic ruthenium(II) phthalocyanines (RuPcs) show potent photodynamic inactivation (PDI) against resistant bacteria like MRSA and E. coli. One RuPc demonstrated synergistic effects with doxycycline against MRSA.

Area of Science:

  • Photodynamic Therapy
  • Antimicrobial Research
  • Materials Science

Background:

  • Multiresistant microorganisms pose a significant global health threat.
  • Traditional antibiotics face challenges due to increasing resistance.
  • Phthalocyanine-based photosensitizers are explored for antimicrobial applications.

Purpose of the Study:

  • To design and evaluate novel multicationic ruthenium(II) phthalocyanines (RuPcs) for photodynamic inactivation (PDI) of multiresistant microorganisms.
  • To investigate the structure-activity relationship of RuPcs with varying cationic charges and amphiphilic properties.
  • To assess the efficacy of RuPcs against Gram-positive (MRSA), Gram-negative (E. coli), and fungal (C. albicans) pathogens.

Main Methods:

  • Synthesis of four RuPcs (PS1a-PS4a) with 4-12 terminal ammonium salts.
  • Evaluation of PDI efficacy under low light conditions.
  • Assessment of antimicrobial activity against MRSA, E. coli, and C. albicans.
  • Investigation of synergistic effects with subinhibitory doxycycline doses.

Main Results:

  • Hydrophilic PS1a, PS2a, and amphiphilic PS3a demonstrated superior PDI activity against MRSA compared to conventional phthalocyanines.
  • PS1a, PS2a, and PS3a exhibited high activity against E. coli.
  • PS4a showed limited activity alone but a significant synergistic effect with doxycycline against MRSA, enhancing log reduction.
  • Weak fungicidal activity was observed against fluconazole-resistant C. albicans.

Conclusions:

  • Multicationic RuPcs are effective photosensitizers for PDI of resistant bacteria.
  • Amphiphilic properties and cationic charge influence RuPc localization and efficacy.
  • RuPcs offer a promising alternative or adjunct therapy for combating multidrug-resistant infections.

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