Antifungal agents: mechanisms of action.
Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied changes in therapeutic immunosuppressive therapies. The search for new molecular targets for antifungals has generated considerable research using modern genomic approaches, so far without generating new agents for clinical use. Meanwhile, six new antifungal agents have just reached, or are approaching, the clinic. Three are new triazoles, with extremely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wall polysaccharides--a new mode of action. In addition, the sordarins represent a novel class of agents that inhibit fungal protein synthesis. This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential.
Odds
Frank C
FC
Aberdeen Fungal Group, University of Aberdeen, Department of Molecular and Cell Biology, Institute of Medical Sciences, Aberdeen AB25 2ZD, UK. f.odds@abdn.ac.uk
Brown
Alistair J P
AJ
Gow
Neil A R
NA
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D054714:Echinocandins; D005656:Fungal Proteins; D005658:Fungi / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D007192:Indenes; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides; D010456:Peptides, Cyclic; D013261:Sterols / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D007192:Indenes; D010455:Peptides; D010456:Peptides, Cyclic; D013261:Sterols; C003329:sordarin; C007572:echinocandin B