Researchers develop new antifungal compounds with improved safety profile
pharmafile | July 29, 2026 | News story | |Â Â The University of Manchester, antifungal therapies, imperial college londonÂ
Researchers at Imperial College London and The University of Manchester have developed a new family of antifungal compounds that demonstrated greater potency and lower toxicity than existing treatments in preclinical studies, offering a potential new approach to tackling drug-resistant fungal infections.
Published in Nature, the research describes enzyme-engineered polyene antifungal agents that were shown to outperform established therapies in mouse models while reducing harmful side effects.
Fungal infections are becoming increasingly difficult to treat as resistance to existing medicines grows and the pipeline of new antifungal therapies remains limited. Current polyene drugs, including amphotericin, are highly effective but can cause significant toxicity because fungal cells share many similarities with human cells.
Using genome mining, the researchers identified bacterial species capable of producing previously undiscovered polyene compounds before applying nuclear magnetic resonance techniques to determine their structures and generate a library of derivatives for testing. Several candidates demonstrated improved antifungal activity, reduced toxicity and better solubility than existing compounds.
One compound, known as Nys34, produced particularly encouraging results. In a mouse model of invasive aspergillosis, it reduced fungal burden without significant signs of toxicity. Researchers also found that Nys34 acts through a different mechanism from amphotericin, suggesting it could help treat fungal pathogens that have developed resistance to existing therapies.
Professor Jason Micklefield, who led the project, said: “We found that one of the most effective new polyene derivatives, Nys34, has a different mode-of-action to the widely used amphotericin. Because Nys34 kills fungal cells in a different way, it could prove very useful to combat emerging pathogens that have evolved resistance to amphotericin.”
The team developed an enzyme-based manufacturing approach that avoids the complex chemical synthesis traditionally required to modify polyene drugs. The researchers believe the process could provide a scalable and cost-effective route to developing improved antifungal medicines, with further work planned to advance Nys34 towards clinical testing.
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