Inhibition of Mammalian Mitochondrial Protein Synthesis by Oxazolidinones
ABSTRACT
MATERIALS AND METHODS
Isolation and incubation of mitochondria from rat and rabbit heart and rat liver.
Preparation of rabbit bone marrow mitochondria.
Mitochondrial protein synthesis assay.
Determination of MIC.
Determination of respiratory control ratios.
Materials.
RESULTS
Rat toxicity of oxazolidinones.
Time course of incorporation and dose-response curves.
Effect of clinically approved antibiotics on mitochondrial protein synthesis.
Effect of oxazolidinones on mitochondrial protein synthesis.
The effect of oxazolidinones on mitochondrial protein synthesis is stereospecific.
Correlation of oxazolidinone inhibition of mitochondrial translation with antibiotic potency.
Effects of oxazolidinones on mitochondrial protein synthesis in mitochondria from rabbit bone marrow.
DISCUSSION
Compound | IC50 (μM) |
---|---|
5S compounds | |
PNU-177553 | 1.1 ± 0.2 |
Eperezolid | 4.2 ± 0.4 |
PNU-141659 | 3.7 ± 0.2 |
PNU-179759 | 0.8 ± 0.2 |
5R compounds | |
PNU-184414 | 161 ± 46 |
PNU-107112 | 181 ± 48 |
PNU-184415 | Not detected |
PNU-244967 | 65 ± 8 |
Oxazolidinonea | IC50 (μM) for tissue: | ||||
---|---|---|---|---|---|
Rat heart | Rabbit heart | Rabbit bone marrow | |||
PNU 97786 | 1.1 ± 0.3 | 1.2 ± 0.1 | 2.5 ± 0.3 | ||
PNU-93936A | 2.1 ± 0.4 | 2.9 ± 0.3 | 6.8 ± 1.4 | ||
Eperezolid | 4.2 ± 0.4 | 5.7 ± 1.4 | 14.9 ± 1.9b | ||
PNU-100480 | 11.8 ± 0.6 | 8.3 ± 1.0 | 18.6 ± 2.9b | ||
PNU-143702 | 184 ± 24 | 77 ± 10 | 192 ± 36 |
Acknowledgments
REFERENCES
Information & Contributors
Information
Published In
Copyright
History
Contributors
Metrics & Citations
Metrics
Note:
- For recently published articles, the TOTAL download count will appear as zero until a new month starts.
- There is a 3- to 4-day delay in article usage, so article usage will not appear immediately after publication.
- Citation counts come from the Crossref Cited by service.
Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.