Fluoroquinolones are orally administered and well tolerated drugs and are increasingly used effectively to combat various systemic infections as well as urinary tract infections. However, fluoroquinolones are not as useful as desired in some therapeutic applications particularly respiratory infections due to low activity against streptococci and enterococci. More active and broader spectrum antibacterial drugs are greatly needed. The effect of the 2-benzoxazolyl group and 5-substituted 2-benzoxazolyl groups at the C7 position upon the activity of fluoroquinolones will be investigated. The groups substituted at the five position of the benzoxazole ring will be chloro, methyl, nitro and amino. The proposed compounds may represent dual mechanisms of antibacterial action since some 2,5 disubstituted benzoxazoles have shown significant activity and may address the problem of development of resistance among currently available fluoroquinolones. This study will yield valuable information necessary for the design of more effective drugs for the treatment of various kinds of bacterial infections. The synthesis of the proposed fluoroquinolones will be accomplished by condensation of 2-fluoro-5-aminobenzoic acid with the appropriately substituted o-aminophenol to yield the corresponding aminophenylbenzoxazole followed by use of the Gould-Jacobs synthetic path to quinolones. The amino substituted fluoroquinolone is obtained from the nitro compound by reduction of the nitro group. In vitro tests will be accomplished by a broth dilution method versus norfloxacin a clinically used fluoroquinolone, as reference. Antibacterial potency will be measured in terms of the minimum inhibitory concentration (MIC). The bacteria which will be used for in vitro tests are Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus aureus.
| Cheema, Ijaz R; Jones, Donald L (2003) TNF-alpha and cortisone impair peptide chain initiation by altering the availability of initiation factor EIF-4E. Front Biosci 8:s1051-5 |
