Genomics, molecular targets and the discovery of antifungal drugs.
Comparative analyses of fungal genomes and molecular research on genes associated with fungal viability and virulence has led to the identification of many putative targets for novel antifungal agents. So far the rational approach to antifungal discovery, in which compounds are optimized against an individual target then progressed to efficacy against intact fungi and ultimately to infected humans has delivered no new agents. However, the approach continues to hold promise for the future. This review critically assesses the molecular target-based approach to antifungal discovery, outlines problems and pitfalls inherent in the genomics and target discovery strategies and describes the status of heavily investigated examples of target-based research.
Odds
Frank C
FC
Aberdeen Fungal Group, Institute of Medical Sciences, Department of Molecular and Cell Biology, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. f.odds@abdn.ac.uk
D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D065095:Calcineurin Inhibitors; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D005658:Fungi / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D016681:Genome, Fungal; D006801:Humans; D009181:Mycoses / Q000188:drug therapy / Q000382:microbiology; D010597:Pharmacogenetics; D054328:Proton Pump Inhibitors; D059003:Topoisomerase Inhibitors
D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D005656:Fungal Proteins; D054328:Proton Pump Inhibitors; D059003:Topoisomerase Inhibitors; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase