ANTI FUN-GAL: Antifungal Prodrugs to Evade Drug Resistance Faculty of Science, Charles University

Project Summary:

Invasive fungal infections are difficult to treat due to the increasing resistance of fungal species to current treatment and the limited number of available antifungal drugs.1,2 In December 2022, World Health Organization (WHO) published the first list of priority fungal infections threatening public health.3 Pathogenic fungi cause the most significant burden among susceptible individuals, e.g., immunocompromised, organ transplants, or cancer patients. Presence of fungal strains resistant to clinically used antifungals represents the biggest challenge of current decade. Fungal pathogens use several mechanisms leading to drug resistance ranging from drug efflux to chromosomal duplication or target site mutation.4,5 Moreover, resistant invasive mycoses can also develop secondary resistance in response to the current treatment.6,7 Several species (e.g., Aspergillus) have reduced susceptibility to the currently used antifungal drugs resulting in pan-resistance. Prodruging current antifungal drugs overrides toxicity of drugs and drug resistance of fungal pathogens by circumventing common biological barriers, and consequently saves time and money in developing new chemical entities.

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