4- Quinolones, antibacterial action

Features of antibacterial action of derivatives of 4-quinolone-3-carboxylic acid 93KFZ(5)4. 

Maxwell A, Critchlow SE. Mode of action. In Quinolone Antibacterials. Kuhlmann J, Dalhoff A, Zeiler H-J (Eds.) Springer Berlin, Heidelberg,... 

Lomefloxacin and quinolone agents in general are known to exert their antibacterial action by antagonism of the enzyme DNA gyrase also known as bacterial topoisomerase II. DNA gyrase has also been shown to play an important role in the mechanism of bacterial resistance to these agents (30). 

Antibacterial action of quinolones From target to network 13EMC (66)555. 

The difference in activity for R- and -enantiomers of 7-(3-methylpiperazin-l-yl)quinolones, obtained from the corresponding (R)- and (5)-f-butyl-2-methylpiperazin-l-carboxylates, proved to be in the range from 2 to 64 folds in 52 % of cases [95]. In order to improve transport through biological membranes the piperazine moiety in norfloxacin was modified considerably and compound 26 was obtained [96]. To clarify the mechanism of antibacterial action of fluoroquinolones at the cellular level, two regioisomeric citrate-functionalized derivatives of ciprofloxacin 27a,b [97] (Scheme 14) have been obtained and studied. 

Fadeeva N, Shul gina M, Glushkov G (1993) Molecular and biological features of antibacterial action of derivatives 4-quinolon-3-carboxyUc acids. Pharm Chem J 27 4-9... 

In essence, the cephalosporin acts as a carrier (63) for the quinolone. The quinolone is replaced in the bacterial ceU after the action of P-lactamase on the cephalosporin portion of the molecule. This codmg combination represents a relatively new class of antibacterial agents which appear to offer advantages over the separated components (64). A good introductory discussion of these exciting agents can be found (65) (see also Antibiotics P-lactams ... 

Another interesting approach to obtaining potent, broad-spectmm activity has been reported (127). The "dual-action" antibacterial concept involves incorporation of two moieties having complimentary antibacterial modes of action into the same molecule, and uses the mode of action of one part to release the second antibacterial at the site of action. This approach is exemplified in Ro 23—9424 (47) (127), which uses the mode of action and reactivity of the cephalosporin moiety (Fig. 2) to release the quinolone portion. 

Nalidixic acid, the first antibacterial quinolone (Figure 46-3), was introduced in 1963. It is not fluorinated and is excreted too rapidly to be useful for systemic infections. Oxolinic acid and cinoxacin are similar in structure and function to nalidixic acid. Their mechanism of action is the same as that of the fluoroquinolones. These agents were useful only for the treatment of urinary tract infections and are rarely used now, having been made obsolete by the more efficacious fluorinated quinolones. 

The tertiary structure of DNA is often neglected or ignored, but it is important to the action of the quinolone group of antibacterial agents (Chapter 10). The double helix is... 

The quinolones inhibit DNA gyrase, an enzyme that is essential for bacterial replication (Table 7.9). This is the only class of antibacterials that acts by inhibiting a DNA enzyme. Inhibition of DNA enzymes is a common mechanism of action however, for antiviral and anticancer drugs. 

Quinolones are known antibacterial agents which represent a class of highly potent, broad-spectrum antibiotics. Their mode of action is believed to involve inhibition of DNA gyrase, and more recently they have been shown to have in vitro activity against M. Tuberculosis. ... 

During the last two decades a lot of attention has beoi paid to develqmait of double mechanism antibiotics. One of plausible tQtproaches to such compounds is esterification of fluoroquinolone carboxylic adds with derivatives of cqthalospain andpatidllin. Such combination allows one to expand a spectrum of antibacterial activity of beta-lactams conjugated with quinolones due to complementary mechanisms of their actions [7,72]. 

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