Studies on macrolide antibiotics I. Synthesis and antibacterial activity of erythromycin A 9-O-substituted oxime ether derivatives against Mycobacterium avium complex
| Autor: | Shinobu Ohmoto, Satoshi Yoshizumi, Ken Narita, Hideo Kato, Noriyuki Kado, Toshihiko Yoshida, Eichi Okezaki, Akemi Nishimoto, Yoshie Takahashi |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Staphylococcus aureus Magnetic Resonance Spectroscopy Chemical Phenomena medicine.drug_class Stereochemistry Antibiotics Erythromycin Quantitative Structure-Activity Relationship DNA Fragmentation Microbial Sensitivity Tests medicine.disease_cause Microbiology chemistry.chemical_compound Clarithromycin Drug Discovery Oximes medicine Antibacterial agent Chemistry Chemistry Physical Aminoglycoside General Chemistry General Medicine Oxime Mycobacterium avium Complex Anti-Bacterial Agents RNA Bacterial RNA Ribosomal Antibacterial activity medicine.drug |
| Zdroj: | Chemicalpharmaceutical bulletin. 49(9) |
| ISSN: | 0009-2363 |
| Popis: | A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics. |
| Databáze: | OpenAIRE |
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