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Molecular Targets for Antifungals in Amino Acid and Protein Biosynthetic Pathways

Summary

This research explores new ways to fight fungal infections by targeting specific enzymes that fungi need to make proteins and amino acids. These enzymes are either absent in humans or work differently, making them ideal targets for developing safer antifungal medications. Impact on everyday life: – Could lead to new treatments for common fungal infections like athlete’s foot and nail infections – May help fight life-threatening fungal infections in immunocompromised patients – Could help overcome growing drug resistance to current antifungal medications – May result in treatments with fewer side effects than current options – Could potentially reduce healthcare costs through more effective treatments

Background

Fungi cause death of over 1.5 million people every year, while cutaneous mycoses are among the most common infections globally. Current antifungal treatments have limitations including toxicity, drug interactions, and growing resistance. There is an urgent need for new antifungal drugs with novel mechanisms of action.

Objective

To review and analyze potential molecular targets for antifungal therapy in amino acid and protein biosynthesis pathways, focusing on enzymes that are unique to fungi and essential for their growth and virulence.

Results

Multiple promising molecular targets were identified in the aspartate family pathway, branched-chain amino acids biosynthesis, aromatic amino acids biosynthesis, and protein synthesis/modification pathways. Several inhibitors showed potent antifungal activity with low toxicity to human cells. Key compounds included RI-331, ethoxysulfuron, CP1, BN-3b, and various sordarin derivatives targeting different enzymes in these pathways.

Conclusion

Enzymes involved in amino acid and protein biosynthesis pathways represent promising targets for novel antifungal drugs. Many inhibitors demonstrate broad-spectrum activity and low toxicity. While some concerns exist about amino acid auxotrophs acquiring nutrients from the environment, the essential nature of these pathways for fungal virulence and their structural differences from human enzymes make them attractive therapeutic targets.
  • Published in:Amino Acids,
  • Study Type:Review,
  • Source: 10.1007/s00726-021-03007-6
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