Sphingolipids as targets for treatment of fungal infections

Future Med Chem. 2016 Aug;8(12):1469-84. doi: 10.4155/fmc-2016-0053. Epub 2016 Aug 9.

Abstract

Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids.

Keywords: antifungals; drugs; fungi; glucosylceramide; sphingolipids; targets.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Fungi / drug effects*
  • Fungi / metabolism*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycoses / drug therapy*
  • Mycoses / microbiology*
  • Sphingolipids / antagonists & inhibitors*
  • Sphingolipids / biosynthesis
  • Sphingolipids / metabolism
  • Virulence / drug effects

Substances

  • Antifungal Agents
  • Sphingolipids