Antifungals that Affect Cell Wall Synthesis

ANTIFUNGALS THAT AFFECT CELL WALL SYNTHESIS

Given the unique chemical nature of the fungal cell wall, with its interwoven layers of mannan, mannoprotein, glucan, and chitin , it is disappointing that agents that act on any component of the cell wall have not yet made an impact in antifungal chemotherapy. The fungal equivalent of the -lactam and glycopeptide inhibitors of bacte-rial peptidoglycan synthesis would be most welcome. One class of agents (echinocandins), which block glucan synthesis by inhibition of glucan synthetase, cause morphologic dis-tortions and osmotic instability in yeast that are similar to the effect ofβ-lactams on bacte-ria. The first such agent to be licensed is caspofungin, which has good activity against Candida and Aspergillus. Another class of compounds (nikomycins), which disrupt chitinsynthesis, are at an earlier stage of development.