Thiopyridinium phthalocyanine for improved photodynamic efficiency against pathogenic fungi
Juliana A Prandini1, Kelly A D F Castro1, Juliana C Biazzotto1
1Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Abstract:
The emergence of opportunistic pathogens and the selection of resistant strains have created a grim scenario for conventional antimicrobials. Consequently, there is an ongoing search for alternative techniques to control these microorganisms. One such technique is antimicrobial photodynamic therapy (aPDT), which combines photosensitizers, light, and molecular oxygen to produce reactive oxygen species and kill the target pathogen. Here, the in vitro susceptibilities of three fungal pathogens, namely Candida albicans, Aspergillus nidulans, and Colletotrichum abscissum to aPDT with zinc(II) phthalocyanine (ZnPc) derivative complexes were investigated. Three ZnPc bearing thiopyridinium substituents were synthesized and characterized by several spectroscopic techniques. The Q-band showed sensitivity to the substituent with high absorptivity coefficient in the 680-720 nm region. Derivatization and position of the rings with thiopyridinium units led to high antifungal efficiency of the cationic phthalocyanines, which could be correlated with singlet oxygen quantum yield, subcellular localization, and cellular uptake. The minimum inhibitory concentrations (MIC) of the investigated ZnPc-R complexes against the studied microorganisms were 2.5 μM (C. albicans) and 5 μM (A. nidulans and C. abscissum). One ZnPc derivative achieved complete photokilling of C. albicans and, furthermore, yielded low MIC values when used against the tolerant plant-pathogen C. abscissum. Our results show that chemical modification is an important step in producing better photosensitizers for aPDT against fungal pathogens.
Insights
Antimicrobial photodynamic therapy (aPDT) offers a novel approach to combat drug-resistant fungi. New zinc(II) phthalocyanine derivatives show potent antifungal activity, demonstrating the potential of chemically modified photosensitizers for aPDT applications.
Area of Science:
- Photochemistry
- Medicinal Chemistry
- Mycology
Background:
- Conventional antimicrobials face challenges from opportunistic pathogens and increasing resistance.
- Antimicrobial photodynamic therapy (aPDT) is an emerging alternative, utilizing photosensitizers, light, and oxygen to generate pathogen-killing reactive oxygen species.
Purpose of the Study:
- To investigate the in vitro antifungal efficacy of novel zinc(II) phthalocyanine (ZnPc) derivatives against key fungal pathogens.
- To explore the structure-activity relationship of ZnPc derivatives in aPDT.
Main Methods:
- Synthesis and spectroscopic characterization of three ZnPc derivatives with thiopyridinium substituents.
- Evaluation of in vitro antifungal activity using minimum inhibitory concentration (MIC) assays.
- Assessment of photodynamic effects, including singlet oxygen quantum yield, cellular uptake, and subcellular localization.
Main Results:
- The synthesized ZnPc derivatives exhibited high absorptivity in the 680-720 nm region.
- Antifungal efficiency correlated with singlet oxygen quantum yield, cellular uptake, and localization.
- MIC values were as low as 2.5 μM for Candida albicans and 5 μM for Aspergillus nidulans and Colletotrichum abscissum.
- One derivative demonstrated complete photokilling of C. albicans and effective activity against the plant pathogen C. abscissum.
Conclusions:
- Chemical modification of ZnPc derivatives enhances their antifungal efficacy for aPDT.
- These novel photosensitizers show promise for developing new strategies against fungal infections.
