Glucan synthase inhibitors as antifungal agents

• Published in: Advances in Protein Chemistry Vol. 56; pp. 423 - 475
• Main Authors: Kurtz, Myra B., Rex, John H.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2001
• Subjects: Antifungal Agents - pharmacology; Biochemistry; Biophysics; Enzyme Inhibitors - pharmacology; Glucosyltransferases - antagonists & inhibitors; Life sciences: general issues
• ISBN: 0120342561; 9780120342563
• ISSN: 0065-3233; 1557-8941
• DOI: 10.1016/S0065-3233(01)56011-8

Fungal infections can range from superficial, noninvasive diseases of normal children and adults to life-threatening systemic diseases of immunocompromised individuals. The novel, fungal-specific mode of action suggests that these compounds may not produce mechanism-based toxicity and can act on fungi that have intrinsic or acquired resistance to currently marketed drugs. Although a linear path from discovery to clinical application is never truly expected, the detours experienced in this journey illustrate the multiple influences that affect the drug discovery process, including changing clinical needs, enabling medicinal chemistry, and a better understanding of the molecular biology of human pathogens. And of course, there is also the powerful, but unreliable factor of serendipity, which can change the road traveled. Ideally, clinicians would like to treat or prevent these wide-ranging fungal infections with a single, nontoxic antifungal agent. Unfortunately, this requires eradication of a very diverse set of eukaryotic microbes from a eukaryotic host. Three groups of agents are used to date: the polyenes, the azoles, and flucytosine. The chapter also looks forward to the development of new compounds as powerful new tools for treating important fungal infections.