Novel small molecules for the treatment of infections caused by Candida albicans: a patent review (2002-2010).
BACKGROUND
The fungal pathogen Candida albicans is one of the leading causes of infections affecting immunodeficient individuals, including those HIV-infected and patients undergoing cancer therapy. Emerging problems in terms of therapeutic efficacy and drug resistance have highlighted the need to consider new therapeutic approaches, based on the exploitation of virulence factors as alternatives to conventional drug targets.


METHODS
Advances in the development of anti-Candida drugs are examined in this review, as reflected by the patent literature since 2002 along with selected peer-reviewed publications. Taking into account a total of 26 patents, the discussion encompasses several therapeutic approaches, including azoles as ergosterol biosynthesis inhibitors, glucan and chitin synthase inhibitors, and secreted aspartyl protease inhibitors.


CONCLUSIONS
New analogs of existing drugs are being developed as broad spectrum antifungals to improve efficacy and circumvent drug resistance. Also, candidate drugs targeting new virulence factors are promising to overcome limitations due to poor efficacy and the rising of drug resistance observed for several available drugs. Efforts for the discovery and development of antifungal agents should be equivalent to other therapeutic areas, and advances in the generation of therapeutic agents with fungus-specific mechanisms of action are of highest priority.
University of Florence, Department of Chemistry Ugo Schiff, Polo Scientifico e Tecnologico, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy.
Chiara
C
Calugi
Andrea
A
Trabocchi
Antonio
A
Guarna
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D002177:Candidiasis / Q000188:drug therapy*; D002687:Chitin Synthase / Q000037:antagonists & inhibitors; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D007192:Indenes / Q000494:pharmacology; D008364:Mannosyltransferases / Q000037:antagonists & inhibitors; D010330:Patents as Topic; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D005656:Fungal Proteins; D007192:Indenes; C003329:sordarin; D005964:Glucosyltransferases; D008364:Mannosyltransferases; C040232:glucan synthase; D002687:Chitin Synthase; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida