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

[摘要] BackgroundProtein farnesylation is an important tosttranslational modification in fungi. We evaluated the antifungal activity of two farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.MethodsDisk 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.ResultsDisk 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.ConclusionThe 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.

[发布日期] 2013-12-05

[关键词] Aspergillus;Candida;Farnesyltransferase inhibitors;Antifungal susceptibility testing