Quinolones are a class of synthetic antibacterial agents that are effective in treating various bacterial infections, including urinary tract infections (UTIs).
They are derived from the parent compound nalidixic acid, which was discovered in the 1960s.
Later generations of quinolones are referred to as fluoroquinolones due to the addition of a fluorine atom at position 6 of the quinolone core structure.
SAR of Quinolones
Structure-activity relationships (SAR) of quinolones are essential for understanding their potency, spectrum of activity, and pharmacokinetic properties.
Key structural features of quinolones and their relationships with antimicrobial activity include:
1. Central ring:
The quinolone core structure consists of a bicyclic system containing a pyridone ring fused to a quinoline ring. The presence of a carbonyl group at position 4 and a carboxylic acid at position 3 are essential for antibacterial activity.
2. Fluorine at position 6:
The addition of a fluorine atom at position 6 on the quinolone core structure greatly enhances the antimicrobial potency and spectrum of activity. This modification results in the fluoroquinolone class of compounds.
3. Substituents at position 7:
The nature of the substituent at position 7 of the quinolone core structure affects the potency and spectrum of activity. Generally, a piperazinyl or similar amine-containing group at position 7 enhances activity against Gram-negative bacteria and atypical pathogens. For example, ciprofloxacin and levofloxacin have a piperazinyl group at this position.
4. Substituents at position 1:
The presence of an alkyl or cycloalkyl group at position 1 of the quinolone core structure is essential for antimicrobial activity. The nature of the substituent at position 1 can affect pharmacokinetic properties, such as oral bioavailability and tissue distribution. For instance, moxifloxacin has a cyclopropyl group at position 1, which contributes to its enhanced activity against Gram-positive bacteria and anaerobes.
5. Substituents at position 8:
The presence of a halogen atom (typically chlorine or fluorine) at position 8 of the quinolone core structure can increase the potency and spectrum of activity against certain bacterial species. However, it can also increase the potential for phototoxicity. Lomefloxacin, for example, has a fluorine atom at position 8, which contributes to its increased activity against Gram-negative bacteria, but it also has a higher risk of phototoxicity compared to other fluoroquinolones.