Antifungal photodynamic activity of porphyrin derivatives bearing aminopropoxy groups

QUIROGA, EZEQUIEL D.; MORA, S. JIMENA, ÁLVAREZ, M. GABRIELA, MILANESIO, M. ELISA, DURANTINI, EDGARDO N.

Córdoba

Encuentro; XI ELAFOT, XI Encuentro Latinoamericano de Fotoquímica y Fotobiología; 2012

Antimicrobial resistance is a growing problem that complicates the treatment of important nosocomial and community-acquired infections. In the last years, resistance of Candida albicans is increasing against traditional antifungal azole derivatives. Hence, it is necessary to develop alternative therapies for the treatment of candidiasis. A promising modality is photodynamic inactivation (PDI) of microorganisms, which uses a combination of light, a photosensitizer and oxygen to achieve a cytotoxic effect in the cells. In the PDI process, the photosensitizer excited reacts with molecular oxygen, generating highly reactive oxygen species that promote death of microorganism. In this study the photodynamic activity of 5,10,15,20-tetrakis [4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and 5,10,15,20-tetrakis [4-(3-N,N,N-trimethylamine propoxy)phenyl]porphyrin (TAPP4+) were compared in presence of fluconazole on Candida albicans. These porphyrins photosensitized the decomposition of L-tryptophan in different media. The quantum yields of singlet molecular oxygen were 0.74 and 0.72 for TAPP and TAPP4+, respectively. The cultures treated with 5 µM porphyrin showed a binding of 1.04 nmol/106 cells for TAPP and 1.50 nmol/106 cells for TAPP4+ after 30 min of incubation. Cell survival with both sensitizers caused a decrease of ~5 log after 30 min irradiation with visible light. Fluconazole is a standard active antifungals established to eradicate C. albicans. The susceptibility of this yeast was evaluated using the lowest concentration of fluconzole (MIC), which inhibits the visible growth of C. albicans after 24 h incubation at 37ºC (range 0.25-1.5 µg/mL). A MIC value of 1.0 µg/mL was found for fluconazole. A decrease of MIC to 0.25 µg/mL was obtained using a combined action of 1 µM porphyrin, 30 min irradiation and fluconazole (0.25-1.5 µg/mL). The growth delay of C. albicans cultures produced by 1µM porphyrin and irradiation was studied in presence of different concentration of fluconazole. Under these conditions, the inactivation effect of PDI-fluconazole was more efficient than the irradiation of the porphyrin or fluconazole alone. The results obtained in the present study indicate that a stronger antifungal activity is produced by PDI-fluconazole and both photosensitizers produced a similar photoinactivation activity. Therefore, these results indicate that PDI combined with an antifungal, such as fluconazole, is an interesting approach to eradicate yeast cells.