In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida

Ann Clin Microbiol Antimicrob. 2013 Dec 5:12:37. doi: 10.1186/1476-0711-12-37.

Abstract

Background: Protein farnesylation is an important tosttranslational modification in fungi. We evaluated the antifungal activity of two farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.

Methods: Disk diffusion assay and broth microdilution assay were used to determine the antifungal susceptibility of two farnesyltransferase inhibitors (manumycin A and tipifarnib) against clinical isolates of Aspergillus and Candida.

Results: Disk diffusion assay demonstrated both agents had activity against Aspergillus and Candida. The minimal inhibitory concentration (MIC) ranges for manumycin A against Aspergillus and Candida were 200 to 400 μM and 13 to >25 μM, respectively. Unfortunately, the MIC were vastly higher than the concentrations that inhibit the proliferation and viability of mammalian cells. The MICs of tipifarnib against Aspergillus and Candida were >1600 μM.

Conclusion: The outcome of present study showed that farnesyltransferase inhibitors have activity against Aspergillus and Candida. This suggests that farnesyltransferase may be used as anifungal target in designing and developing new drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Aspergillosis / microbiology
  • Aspergillus / drug effects*
  • Aspergillus / enzymology
  • Aspergillus / isolation & purification
  • Candida / drug effects*
  • Candida / enzymology
  • Candida / isolation & purification
  • Candidiasis / microbiology
  • Enzyme Inhibitors / pharmacology*
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Humans
  • Microbial Sensitivity Tests
  • Polyenes / pharmacology
  • Polyunsaturated Alkamides / pharmacology
  • Quinolones / pharmacology

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Polyenes
  • Polyunsaturated Alkamides
  • Quinolones
  • Farnesyltranstransferase
  • tipifarnib
  • manumycin