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Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones
Wanessa C M A Melo1, Mariana Bastos Dos Santos2, Beatriz de Carvalho Marques2
1Biociências e Biotecnologia Aplicada a Farmácia/Núcleo Proteomica, Universidade Estadual Paulista, Araraquara-SP, Brazil.
Abstract:
Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL-1) incubated by 15min and irradiated with LED 450nm with 24Jcm-2. Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity.
Insights
Antimicrobial photodynamic therapy using chalcone derivatives effectively inactivated Histoplasma capsulatum. This new strategy shows promise for treating fungal infections with minimal toxicity to host cells.
Area of Science:
- Medical Mycology
- Photodynamic Therapy
Background:
- Histoplasmosis, caused by Histoplasma capsulatum, presents varied clinical manifestations.
- Current treatments like amphotericin B and azoles have limitations, necessitating novel therapeutic approaches.
- Antimicrobial photodynamic therapy (aPDT) is explored as a potential alternative for fungal infections.
Purpose of the Study:
- To determine optimal parameters for selective photoinactivation of Histoplasma capsulatum using chalcone derivatives.
- To compare the efficacy of chalcone-mediated aPDT against H. capsulatum and host cells (fibroblasts, keratinocytes).
Main Methods:
- Development of water-soluble chalcone derivatives as photosensitizers.
- Incubation of H. capsulatum and host cells with chalcones, followed by irradiation with LED light.
- Evaluation of selective inactivation based on photosensitizer concentration, incubation time, and light dose.
Main Results:
- Optimal conditions identified: 1.95μg/mL chalcone concentration, 15-minute incubation, and 450nm LED irradiation at 24J/cm².
- Demonstrated selective photoinactivation of H. capsulatum with minimal impact on fibroblastic and keratinocyte cells.
- Chalcone derivatives showed antifungal activity and high reactive oxygen species (ROS) generation.
Conclusions:
- Chalcone-based aPDT offers a promising, selective strategy for treating Histoplasma capsulatum infections.
- This approach addresses limitations of existing antifungal therapies, including drug resistance and side effects.