The document summarizes key aspects of quinolones including their history, mechanism of action, classification, and details about specific quinolones like ciprofloxacin, norfloxacin, and enoxacin. It discusses how quinolones are synthetic broad-spectrum antibiotics that act by inhibiting bacterial DNA gyrase and topoisomerase enzymes. It also categorizes quinolones into four generations based on their antimicrobial spectrum and lists some common uses and adverse effects.

1. By- Ayushi Dogne
Sri Aurobindo Institute of Pharmacy

2.  Introduction
 History
 SAR of Quinolones
 Mechanism of Action
 Uses of Quinolones
 Classification
 Ciprofloxacin
 Synthesis of Ciprofloxacin
 Norfloxacin
 Enoxacin
Contents

3. Quinolones are synthetic broad –spectrum
Antibiotics.
● Synthetic chemotherapeutic antibacterial.
● Bactericidal in nature.
● Favourable pharmacokinetics.
Increasingly used because of their relative safety,
availability both orally and parentrally .
Introduction

4. ● In 1960, mark the first decade of quinolone development and use.
● In 1964, nalidixic acid was the first compound to be discovered, an antibacterial
byproduct of chlorquine synthesis , bactericidal.
● After 2 years of discovery , it was described to act by inhibiting the synthesis of
bacterial DNA gyrase.
● It was licensed for the treatment of UTIs.
● In 1970s , some derivative of nalidixic acid such as pipemidic acid[first piperzinyl
quinoline], oxolinic acid and cinoxacin were discovered.
● These agents proved minimal improvements over nalidixic acid.
● After extensive clinical use of nalidixic acid,few microoraganisms develop resistance
to it, proved to be a characterstic of early quinolones.
● In 1969,resistance to nalidixic acid in Escherichia coli was mapped due to
chromosomal mutations.
History

5. Nalidixic acid
First therapeutically useful
quinolone active against
gram –ve bacteria.

6. SAR
Of
Quinolones

7. Carboxylic moiety at C-3
Is most common. Other
acidic groups loss
antibacterial activity.
Oxo group at c-4
position essential for
activity.
Replacing C-2
hydrogen is
disadvantageous.
Introducing amino group
at c-5 enhance the
antibacterial activity.
Introduce an F atom
at c-6 does epic work
Reactivity order F >
Cl Br, CH3 > CN.
At C-7 Piperazine
moiety is landmark
development.
At c-8 fluoro substituent is active
against gram -ve bacteria.
C-8 methoxyl moiety active
against gram +ve bacteria.
A halogen (F,Cl) at C-
8 improves oral
absorption.
A compilation of
active N-1
quinolone
substituents shown
overall in vitro
potency.

8. Mechanism of action
3.Following cell
wall entry through
porin channels,
fluoroquinolones
bind to these
enzymes and
interfere with DNA
ligation.
1.Most bacterial
species maintain
two distinct type II
topoisomerases
that assist with
deoxyribonucleic
acid (DNA)
replication.
2.DNA gyrase
{supercoiling} and
Topoisomerase IV
{Unwinding}.
4.This interference
increases the number
of permanent
chromosomal breaks,
triggering cell lysis.FQ
have different targets
for gram-ve and gram-
positive org anisms,
resulting in rapid cell
death.

9. Uses
● Nalidixic acid used as urinary antiseptic.
● Second line drug in recurrent cases or on the basis
of sensitivity reports.
● It has been used in Diarrhoea caused by Proteus,
Ecoli , shigella, or salmonella.
● Fluroquinolones used in urinary tract infection,
Gonorrhoea chanchroid (type of STD)
● Used in respiratory infection and conjuctivitis (pink
eye disease)
Quinolones has the following uses :

10. Adverse effects

11. compounds{norfloxacin, ciprofloxacin,
etc.} possess excellent Gram-negative
activity and good activity against Gram-
positive bacteria.
Second generation
compounds (for example, nalidixic acid)
were narrow spectrum agents with
activity against aerobic gram-negative
bacilli, mostly Enterobacteriaceae.
First generation
Compounds active against
streptococci.
Third generation
Class acts at DNA gyrase and
topoisomerase IV, dual
action slows the
development of resistance
Fourth generation
Classification
Researchers divide the quinolones in
generations based on their anti
bacterial spectrum.

12. classification
Cinoxacin
Flumequine
Nalidixic acid
Oxolinic acid
Piromidic acid
Pipedimic acid
Rosoxacin
Balofloxacin
Levofloxacin
Sparfloxacin
Grepafloxacin
Temafloxacin
tosufloxacin
Clinafloxacin
Gatifloxacin
Gemifloxacin
Moxifloxacin
Sitafloxacin
Trovafloxacin
Ciprofloxacin
Enoxacin
Fleroxacin
Lomefloxacin
Norfloxacin
Nadifloxacin
Ofloxacin
Pefloxacin

13. ● It is a synthetic chemotherapeutic antibiotic of
fluroquinolones class.
● It is second generation antibacterial.
● Bactericidal , interferes with enzymes cause DNA
to rewind after copied , thus blocks DNA and
protein synthesis.
MECHANISM –
Act on bacterial topoisomerase – II(DNA grase) and
topoisomerase –IV. Ciprofloxacin targeting of the alpha
subunits of DNA gyrase prevents it from supercoiling the
bactericidal DNA that prevents DNA replication.
Ciprofloxacin

14. Synthesis

15. ● Used to treat infections of bones and joints, endocarditis,
malignant otitis externa, respiratory tract infections and urinary
tract infections.
● Treatment of serious infections caused by gram – negative bacteria
including Pseudomonas aeruginosa.
● Certain skin infections, acute or chronic prostatis.
USES

16. Synthetic Broad spectrum antibacterial.
Active against gram –ve and gram +ve bateria.
Mechanism - Inhibits topoisomerase II and topoisomerase IV
enzymes that are required for bacterial DNA
replication , transcription ,repair , recombination.
Uses - First line urinary antibacterial .
Useful in genital infection.
Effective in Gonorrhoea, typhoid fever.
prophylaxis in sepsis in neuropenic patients.
Adverse effects – lightheadedness, muscle and joint aches,
Sweating , vaginal itching or discharge
and headache.
Norfloxacin

17.  Broad spectrum antibiotic.
 Orally available
 Antibacterial agent related to nalidix acid.
Mechanism - inhibits DNA gyrase (DNA
topoisomerase II),which is
essential bacterial enzyme.
Uses – used in adults (> 18 yrs of age) for
treating uncomplicated urethral or cervical
Gonorrhoea caused by Neisseria
Gonorrhoeae
Enoxacin

18. Ofloxazin
Lomefloxacin

19. Gatifloxacin
Moxifloxacin

20. THANK YOU