**2. Quinolones: Structural features and method of synthesis**

### **2.1 Structural features**

258 Antimicrobial Agents

The mechanism of action of quinolone antibacterial agents involves the inhibition of DNA

The antibacterial activity of quinolones (measured in terms of MIC), however, is the result of the combination of bacterial cell penetration and DNA gyrase inhibitory activity. The antibacterial activity of quinolones depends not only on the bicyclic heteroaromatic system combining the 1,4-dihydro-4-pyridine-3-carboxylic acid moiety and an aromatic ring, but also on the nature of the peripheral substituents and their spatial relationships. These substituents exert their influence on bacterial activity by providing additional affinity for

The research for an ideal quinolone continues worldwide. Such a quinolone must be biologically active on a large spectrum of gram positive and gram negative bacteria, aerobes and anaerobes and mycobacteria, must have as few side effects as possible, excellent

In figure 5, the most common synthesized chemical variations obtained during the research

**F**

**C2H5, C2H4F, NHCH3, t-Butil**

**S**

**CH3**

**S CH3**

**S NH**

**O**

**S**

**S**

**O**

**CH3**

**CH3 N**

**<sup>O</sup> CH3**

**O**

**S**

**CH3**

**CH3 O N**

> **CH3 N**

**CH3**

**O NH O**

**F**

**N**

**R**

**S**

gyrase (a bacterial topoisomerase II) resulting in a rapid bactericidal effect.

bacterial enzimes, enhancing cell penetration or altering the pharmacokinetics.

**NA**

**R6 COOH <sup>5</sup> OR**

**R1**

**1 2 <sup>3</sup> <sup>5</sup> <sup>4</sup> <sup>6</sup> <sup>7</sup> <sup>8</sup>**

**O**

**O**

solubility in water and oral bioavailability.

**Hal CH3 NH2**

**H**

**N NR**

**NH2**

**N**

**N**

**N**

**NH2 R**

**N R**

**N NH R**

**N**

**R**

**N**

**<sup>R</sup> <sup>N</sup> <sup>N</sup> <sup>R</sup>**

**NH2 N R**

**HN N R**

> **O N R**

**N R**

**CH2NHR N**

**R**

for new quinolones with antibacterial activity, are visible.

**NH2 (8-F) H, Hal.,CH3, OH**

**R7**

**CH, N, CHal, CNO2, CNH2, CCH3, COCH3, CCH2F**

Fig. 5. Structural variations of the most recent quinolones.

Quinolone derivatives are an important class of antibacterial agents with wide action. Basic structure of these compounds (Figure 6) is a bicyclic structure, which contains a ring of type *A* 4-piridinona combined with aromatic or heteroaromatic ring *B.* The ring type *A* 4 piridinona is a ring with absolute necessity: an unsaturation in position 2-3, a free acid function in position 3 and a substituent at nitrogen in position 1.

Fig. 6. Basic structure of quinolones.
