Medicograspers | Pharmacology notes | Notes on Quinolones and Fluoroquinolones part 1 |

 

Quinolones and fluoroquinolones - part 1

In this article, you will learn about what is quinolones and fluoroquinolones and mechanism by which they exhibit their bactericidal effect. 

Quinolones and fluoroquinolones both are antibiotics.

Quinolones have their key component called Nalidixic acid which is also the key component of fluoroquinolones. Quinolones are said to be effective against gram-negative bacteria.

Fluoroquinolones – a fluorinated form of quinolones is called fluoroquinolones and they are more effective and widely used nowadays.

The fluoroquinolones have the 5 key features which make them more compatible:

1.         This class of drugs has a good oral absorbing capacity.

2.         This class of drugs deeply penetrates the tissues. They can be penetrated to the intracellular component of the cell. So, this class of drugs can eliminate the intracellular organisms causing diseases like chlamydia, TB, Legionella, etc.

3.         Newly synthesized fluoroquinolones are broad-spectrum.

4.         This class of drugs has high potency.

5.         In terms of safety measures, this class of drugs does not produce many side effects comparing to other antibiotics.

Mechanism of action of fluoroquinolones:

To understand the mechanism of action of fluoroquinolones, one must know how the bacteria are undergoing the replication process in DNA and how they effectively keep on growing using this replication process.

•          The bacterial DNA is double-stranded and two strands are generally wrapped together.

•          To make a new DNA strand, the bacterial double-stranded DNA unwrap at the center and make the end of the double-strand to be tightly wrapped.

•          This tight wrapping of two strands at the end of the DNA, is not good for replicating the whole DNA strand.

•          So, nature has provided the bacteria with the enzyme called Topoisomerase aka DNA gyrase (type – 2, in Gram-negative bacteria).

•          This topoisomerase (type – 2) enzyme has two domains. One domain is called the nuclease domain and another one is called the Ligase domain.

•          This nuclease domain cuts the tightly wrapped double-stranded DNA at the edges so that the tight wrapping is relieved at the ends and after DNA replication took place throughout the DNA, the Ligase domain effectively reseals the cut pieces at the ends of the DNA. So, this topoisomerase is changing only the configuration/twist/ topology of the DNA. Thus, this enzyme got its name called Topoisomerase.  This is how the bacteria is effectively undergoing the replication process.

•          Anyway, we are not going to allow the bacteria to be happy as it is giving trouble to us. So, we produced the antibiotics class called fluoroquinolones, which will go and bind to the ligase part of the Topoisomerase (type-2).

•          This leaves the bacteria to be broken down into small pieces but no availability of ligase enzyme to reseals them again. This effectively kills the bacteria by interfering with their DNA replication process.

•          Thus, fluoroquinolones are bactericidal drugs (most are effective against gram-negative bacteria).

 

Technical terms:

Tight wrapping at the ends – positive supercoiling at the ends

After cutting by nuclease – negative supercoiling at the ends

Cutting – nicking

 

Newly synthesized Fluoroquinolones are effective against gram-positive bacteria too!

In gram-positive bacteria, these fluoroquinolones interfere with the enzyme called topoisomerases (type – 4).