title: In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.
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.
  
  
  CONCLUSIONS
  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.
authors: Jianjun
authors: J
authors: Qiao
authors: Peiping
authors: P
authors: Gao
authors: Xiaoling
authors: X
authors: Jiang
authors: Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No, 79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China. fanghongzy@sina.com.
authors: Hong
authors: H
authors: Fang
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D002175:Candida / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib; C054474:manumycin