Version 1
: Received: 16 October 2024 / Approved: 17 October 2024 / Online: 17 October 2024 (11:56:14 CEST)
How to cite:
Pacheco, M. I.; Guimarães, B.; Pereira-Silva, P.; Costa-Barbosa, A.; T. Gonçalves, M. S.; Sousa, M. J.; Sampaio, P. Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species. Preprints2024, 2024101391. https://doi.org/10.20944/preprints202410.1391.v1
Pacheco, M. I.; Guimarães, B.; Pereira-Silva, P.; Costa-Barbosa, A.; T. Gonçalves, M. S.; Sousa, M. J.; Sampaio, P. Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species. Preprints 2024, 2024101391. https://doi.org/10.20944/preprints202410.1391.v1
Pacheco, M. I.; Guimarães, B.; Pereira-Silva, P.; Costa-Barbosa, A.; T. Gonçalves, M. S.; Sousa, M. J.; Sampaio, P. Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species. Preprints2024, 2024101391. https://doi.org/10.20944/preprints202410.1391.v1
APA Style
Pacheco, M. I., Guimarães, B., Pereira-Silva, P., Costa-Barbosa, A., T. Gonçalves, M. S., Sousa, M. J., & Sampaio, P. (2024). Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species. Preprints. https://doi.org/10.20944/preprints202410.1391.v1
Chicago/Turabian Style
Pacheco, M. I., Maria João Sousa and Paula Sampaio. 2024 "Combining Fluconazole with Benzo[a]phenoxazine Derivatives as a Promising Strategy Against Fluconazole-Resistant Candida Species" Preprints. https://doi.org/10.20944/preprints202410.1391.v1
Abstract
The rise of non-albicans Candida species, exhibiting unpredictable antifungal resistance, complicates treatment and contributes to the growing threat of invasive, life-threatening infections. This study evaluated the antifungal activity of four benzo[a]phenoxazine derivatives (C34, C35, A42, and A44) against 14 Candida strains following EUCAST standards. Fluconazole interactions were analysed through fractional inhibitory concentration index (FICI) calculation and response surface analysis, based on the Bliss model. Macrophage-like J774A.1 cells were used to assess Candida killing in the presence of synergistic compounds. The MIC values against the different strains varied, with C34 showing the strongest activity, followed by C35, while A42 had the highest MIC values, indicating lower efficacy. However, A42 demonstrated the best synergy with fluconazole against fluconazole-resistant Candida strains. Cytotoxicity assays revealed that the chloropropyl group present in C35 and A42 enhanced cytocompatibility. Co-culture with macrophages showed significant yeast killing for C. albicans and C. auris when fluconazole and A42 were combined, requiring concentration 4- and 16 times lower than their MIC values, enhancing antifungal activity. Given fluconazole's fungistatic nature and the emergence of drug-resistant strains, benzo[a]phenoxazine derivatives' ability to enhance fluconazole's efficacy presents a promising strategy to address antifungal resistance in critical pathogens. These findings align with global research priorities, offering new potential avenues for developing more effective antifungal therapies.
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
