If these findings are confirmed in further preclinical studies, it could lead to a first-in-class antifungal that works where existing drugs fail. This work shows that it is possible to re-engineer azoles using modern medicinal chemistry to tackle one of the most urgent drug resistance challenges in fungal infections.”
Miraz Rahman, Professor of Medicinal Chemistry
02 July 2025
Antifungal discovery offers hope against deadly drug-resistant infections
Scientists at King’s have developed a new class of antifungal compounds that could offer a powerful weapon against the rising threat of Candida auris, an emerging multidrug-resistant fungus spreading through hospitals worldwide.
Candida auris is a dangerous fungal pathogen that has become a global health concern. It spreads easily in healthcare settings and can cause life-threatening infections, especially in patients with weakened immune systems. Alarmingly, it is often resistant to multiple antifungal drugs, making treatment difficult. The U.S. Centers for Disease Control and Prevention (CDC) reports that over 30% of patients with this bloodstream infection die within 30 days. Both the CDC and the World Health Organisation (WHO) now classify Candida auris as a serious global threat.
Unlike bacteria, fungi share many cellular features with humans, which limits the number of drug classes available. Currently, only four main types of antifungal drugs exist—azoles, polyenes, echinocandins, and pyrimidine analogues—leaving few options when resistance develops.
In the study, published in the Journal of Medicinal Chemistry, researchers led by Professor Miraz Rahman modified the structure of azole antifungals to overcome the common resistance mechanisms in Candida auris including efflux mediated resistance. These new molecules showed strong activity in lab and preclinical studies, even against strains that no longer respond to fluconazole or voriconazole - two widely used antifungal medicines. Researchers from the Rahman group collaborated with UKHSA researchers led by Professor Mark Sutton for this study.
The compounds demonstrated superior ability to enter fungal cells, inhibit key enzymes, and even disrupt fungal biofilms, which are protective layers that make infections harder to treat. In preclinical models, the compound protected infected hosts with no observed toxicity at therapeutic doses. King’s has subsequently filed two patents for these compounds.
This discovery is especially significant for patients at risk of invasive fungal infections, including those in intensive care units or undergoing cancer treatment. New therapies that retain potency where others fail could reduce mortality and limit the spread of resistant strains in hospitals.
The project was supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the UK Health Security Agency (UKHSA).
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Professor of Medicinal Chemistry