Enzymatic 2'-N-Acetylation of Arbekacin and Antibiotic Activity of Its Product
| Autor: | Chun-Bao Zhu, Shinichi Kondo, Yoko Ikeda, Kunimoto Hotta, Jun Ishikawa, Aisuko Sunada, Satoshi Mizuno, Tetsu Ogata |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Dibekacin
medicine.drug_class Acylation Antibiotics Microbial Sensitivity Tests Biology Structure-Activity Relationship Acetyltransferases Drug Discovery N acetylation medicine Arbekacin Pharmacology chemistry.chemical_classification Molecular Structure Strain (chemistry) Aminoglycoside Acetylation Streptomyces Anti-Bacterial Agents Aminoglycosides Enzyme chemistry Biochemistry Antibacterial activity medicine.drug |
| Zdroj: | The Journal of Antibiotics. 49:458-464 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.49.458 |
| Popis: | Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|