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Published on: May 21, 2019
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.
Abstract:
Four photosensitizers PS1a-PS4a consisting in multicationic ruthenium(II) phthalocyanines (RuPcs) have been evaluated in photodynamic inactivation (PDI) of multiresistant microorganisms. The RuPcs, bearing from 4 to 12 terminal ammonium salts, have been designed to target the microorganisms cytoplasmic cell membrane and display high singlet oxygen quantum yields. In addition, PS3a and PS4a were conceived to exhibit multi-target localization by endowing them with amphiphilic character, using two different structural approaches. Under low light regimes, the two hydrophilic PS1a and PS2a, as well as the amphiphilic PS3a show much stronger response against Gram-positive MRSA than that observed for the typical phthalocyanines designed for PDI, namely zinc(II) and palladium(II) complexes, as well as free-base Pcs. Besides, PS1a, PS2a and PS3a show remarkably high activity against the Gram-negative E. coli, although weak fungicidal character against fluconazole-resistant C. albicans. Contrasting, the structurally different, amphiphilic PS4a shows only slight activity for Gram-positive bacteria, despite its ability to cross cell membrane and reach internal organelles. Still, PS4a shows a positive synergistic effect against MRSA when combined with doxycycline, exhibiting an increased activity from about 1.5 to about 4.9 log reduction under the light dose of 30 J/cm2 and the 0.125 mg/L subinhibitory dose of doxycycline.
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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