Fluoroquinolones are orally administered and well tolerated drugs and are increasingly used affectively to combat various systemic infections as well as urinary tract infections. However, the 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 drugs are greatly needed. The effect of the imidazo [1,2-a] pyridin-2-yl group and 6-substituted imidazo [1,2-a] pyridin-2-yl groups at the C7 position upon the activity of fluoroquinolones will be investigated. The groups substituted at the six position of the imidazo [1,2-a] pyridine ring will be chloro, bromo, cyano, carbamoyl, methyl, carboxyl, acetamido and amino groups. Structure- activity anti-bacterial relationships will be determined. This study will aid in defining the optimum C7 group necessary for the design of more active and broader spectrum fluoroquinolone drugs for the treatment of various kinds of bacterial infections. The synthesis of the proposed fluoroquinolones will be accomplished by us of the Gould-Jacobs synthetic path to quinolones. In vitro tests will be accomplished by a broth dilution method versus norfloxacin, a clinically used fluoroquinole, 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 |
