Invention:
This technology includes novel compounds that selectively inhibit fungal dihydroorotate dehydrogenase (DHODH), an essential enzyme in pyrimidine biosynthesis. These inhibitors are active against a range of fungal pathogens, including Cryptococcus neoformans and Candida auris, while sparing the human version of the enzyme. This selectivity reduces the risk of toxicity and offers a new approach to treating difficult fungal infections.
Background:
Fungal diseases require greater attention due to the limited number of antifungal drug classes and the increasing prevalence of drug resistance. Research focused on new targets is crucial for managing resistance to existing treatments. Dihydroorotate dehydrogenase (DHODH) is a key enzyme that catalyzes the conversion of dihydroorotate to orotate in the de novo pyrimidine synthesis pathway, which is essential for DNA and RNA synthesis. DHODH inhibitors are important for combating fungal infections because they disrupt a critical pathway in fungal cells essential for their growth and survival.
Applications:
- Cryptococcosis therapeutics
- Antifungal drug development
- Infectious disease research
Advantages:
- Selective inhibition of fungal DHODH with minimal impact on DHODH
- Compatible with combination therapy
- Potential applications for broader antifungal development
