2-Amino-nonyl-6-methoxyl-tetralin muriate inhibits sterol C-14 reductase in the ergosterol biosynthetic pathway
| Autor: | Hui Tang, Shi-hua Wang, Yi Xu, Hong-tao Liu, Yuan-Ying Jiang, Kai-hua Fan, Yong-Bing Cao, Rong-mei Liang, Ping-Hui Gao, Bao-di Dai, Yong-hong Tan, Youjun Zhou |
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| Rok vydání: | 2009 |
| Předmět: |
Azoles
Male Antifungal Agents BALB 3T3 Cells Tetrahydronaphthalenes Microbial Sensitivity Tests Biology Reductase chemistry.chemical_compound Minimum inhibitory concentration Inhibitory Concentration 50 Mice Biosynthesis Ergosterol Candida albicans Animals Humans Pharmacology (medical) IC50 Pharmacology General Medicine biology.organism_classification Sterol Enzyme assay Biosynthetic Pathways Up-Regulation Sterols chemistry Biochemistry biology.protein Hepatocytes Original Article Oxidoreductases |
| Zdroj: | Acta pharmacologica Sinica. 30(12) |
| ISSN: | 1745-7254 |
| Popis: | To investigate the action mechanism of a novel chemical structural aminotetralin derivate, 2-Amino-Nonyl-6-Methoxyl-Tetralin Muriate (10b), against Candida albicans (C albicans) in the ergosterol biosynthetic pathway.Antifungal susceptibility test of 10b was carried out using broth microdilution method, the action mechanism of 10b against C albicans was investigated by GC-MS spectrometry and real-time RT-PCR assay, and cytotoxicity of 10b in vitro was assessed by MTS/PMS reduction assay.10b reduced the ergosterol content markedly, and the 50% ergosterol content inhibitory concentration (ECIC(50) value) was 0.08 microg/mL. Although the sterol composition of 10b-grown cells was completely identical with that of erg24 strain, the content of ergosta-8,14,22-trienol in 10b-grown cells was much higher than that in erg24 strain. Real-time RT-PCR assay revealed a global upregulation of sterol metabolism genes. In addition, the 50% inhibitory concentration (IC(50) value) of 10b was 11.30 microg/mL for murine embryonic fibroblasts and 35.70 microg/mL for human normal liver cells.10b possessed a mode of action different from that of azoles and morpholines, whose targets were sterol C-14 reductase (encoded by ERG24 gene) and sterol C-5 desaturase (encoded by ERG3) related enzyme. Although 10b seemed to reduce MTS/PMS reduction in a dose dependent manner, IC(50) value for mammalian cells was much higher than 50% minimum inhibitory concentration (MIC(50)) value for C albicans. This indicates that the formulation is preliminarily safe and warrants further study for possible human applications. |
| Databáze: | OpenAIRE |
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