Drug resistant fungi are a growing problem worldwide. Cell Chemical Biology published (Iyer, K. R., et al. (2023) Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity. Cell Chemical Biology) a study by RIKEN Center for Sustainable Research Science (CSRS) and the University of Toronto have discovered a new way to attack fungal infections. The key is to block fungi from being able to make fatty acids, the major component of fats. Currently, there are only three major classes of antifungal medications, and all of them work by destroying the barrier that surrounds fungal cells. A compound named NPD6433 was the least toxic to human cells and reduced the growth of Aspergillus fumigates. The researchers looked at how much NPD6433 suppressed growth in yeast when the yeast was missing one copy of the gene. They found that reduction in only one gene, fatty acid synthase, made yeast more susceptible to NPD6433. This result meant that NPD6433 likely works by inhibiting fatty acid synthase and thus prevents fatty acids from being made inside fungal cells. Further experiments showed that NPD6433 and cerulenin, another fatty acid synthase inhibitor, were able to kill numerous yeast species in culture. Tests showed that treating infected worms with NPD6433 reduced fatalities by about 50%. Importantly, this was true in worms infected with yeast resistant to standard antifungal medication. @ https://www.news-medical.net/news/20230731/New-way-to-attack-fungal-infections-discovered.aspx
