Higher concentration of Fluoroquinolones induce DNA damage by inhibiting human topoisomerase IIα activity. Fluoroquinolones also cause DNA damage by DNA oxidation and inhibition human topoisomerase IIα, in presence of Ultraviolet rays.

1. FLUOROQUINOLONES
ASSOCIATED
PHOTOGENOTOXICITY
Dr. P.Naina Mohamed
Pharmacologist

2. FLUOROQUINOLONES
Structurally Quinolones contain a quinoline ring
system and hence given the name quinolones.
 Fluoroquinolones also contain a fluorine atom at the
6-position of the quinoline ring to increase the
potency.
 Fluoroquinolones and quinolones are not used for
regular treatment of bacterial infections due to their
severe side effects in rare cases.
 They are generally used for more resistant strains
of bacteria and are especially useful in
genitourinary infections.


3. MECHANISM OF ACTION
Fluoroquinolones
Bind to the A-subunit of DNA gyrase (topoisomerase II
type) enzyme
Prevents the binding of substrate to the active site of DNA
gyrase
Absence of formation of enzyme – substrate complex
Blockade of unwinding of double-stranded DNA into a
single stranded structure
Prevention of synthesis of mRNA
Inhibition of bacterial protein synthesis
Antibacterial activity

4. GRAM-POSITIVE AND GRAM-NEGATIVE
BACTERIAS

Gram-positive bacterias:


Fluoroquinolones inhibit DNA gyrase (topoisomerase
II), which is responsible for supercoiling of gram-positive
bacterial DNA during DNA replication.
Gram-negative bacterias:

But, in case of gram-negative
bacteria, Fluoroquinolones inhibit topoisomerase IV, an
enzyme responsible for relaxation of supercoiled circular
DNA and separation of the inter-linked daughter
chromosomes.

5. DNA DAMAGE
Fluoroquinolones (High dose)
Direct binding of quinolones to DNA
Inhibition of topoisomerase IIα activity
Enhanced pre- and post-strand DNA breaks
DNA damage

6. PHOTOGENOTOXICITY
Fluoroquinolones +
Ultraviolet A (UVA) radiation
Formation of reactive oxygen species
DNA oxidation
Increased binding of Fluoroquinolones to both the topoisomerase IIα and the
DNA
Inhibition of human topoisomerase IIα
Prevention of topoisomerase IIα from recognizing and ligating DNA cleaved sites
Enhanced pre- and post-strand DNA breaks
DNA damage

7. REFERENCES
http://toxsci.oxfordjournals.org/con
tent/69/1/16.full
http://www.ncbi.nlm.nih.gov/pubm
ed/14769204
http://www.chinaphar.com/16714083/25/171.pdf