临床分离的曲霉菌和念珠菌的法呢基转移酶抑制剂的体外抗真菌活性。
In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.
机构信息
Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No, 79, Qingchun Road, Hangzhou, Zhejiang Province 310003, China.
出版信息
Ann Clin Microbiol Antimicrob. 2013 Dec 5;12:37. doi: 10.1186/1476-0711-12-37.
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.
背景
蛋白质法尼基化是真菌中一种重要的翻译后修饰。我们评估了两种法尼基转移酶抑制剂对临床分离的曲霉菌和念珠菌的抗真菌活性。
方法
采用纸片扩散法和肉汤微量稀释法测定两种法尼基转移酶抑制剂（曼诺霉素 A 和替匹法尼）对临床分离的曲霉菌和念珠菌的抗真菌敏感性。
结果
纸片扩散法显示两种药物均对曲霉菌和念珠菌有活性。曼诺霉素 A 对曲霉菌和念珠菌的最小抑菌浓度（MIC）范围分别为 200 至 400 μM 和 13 至>25 μM。不幸的是，MIC 远远高于抑制哺乳动物细胞增殖和活力的浓度。替匹法尼对曲霉菌和念珠菌的 MIC 均>1600 μM。
结论
本研究结果表明，法尼基转移酶抑制剂对曲霉菌和念珠菌有活性。这表明法尼基转移酶可能作为设计和开发新药的抗真菌靶标。
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