Quinolones are a class of broad-spectrum antibacterial drugs that act by inhibiting bacterial DNA gyrase and topoisomerase IV, preventing DNA replication. Some key quinolones include nalidixic acid, the first marketed quinolone used for urinary tract infections, norfloxacin which was the first fluorinated quinolone with improved gram-positive activity, and ciprofloxacin which has a broad spectrum of uses. Other quinolones discussed are ofloxacin, lomefloxacin, sparfloxacin, gatifloxacin, and moxifloxacin, each with varying spectrums of activity and indications. Nitrof

1. QUINOLONES
Raj K. Prasad (Gold Medalist)
M. Pharm. (Pharmaceutical
Chemistry)

2. Introduction
• Quinolones are potent, broad-spectrum
antibacterial agents.
• The first representative of the new
class of antimicrobial drugs (called
drugs of the quinolone series, which are
derivatives of naphthyridine)
• These drugs act by inhibiting DNA
gyrase (topoisomerase II) and
topoisomerase IV resulting in the
inhibition of DNA replication.

3. CLASSIFICATION

4. Mode of action:
This action is accomplished by modifying the topology of DNA
via supercoiling and twisting of these macromolecules to
permit DNA replication or transcription.
This enzyme is responsible for supercoiling and compacting
bacterial DNA molecules into the bacterial cell during
replication.
Quinolones inhibit the action of bacterial DNA gyrase
enzyme.

5. SAR OF QUINOLONES

6. • The optimum substituents at
position 1 appear to be ethyl,
butyl, cyclopropyl, and Addition
of a fluorine atom into the N-1
cyclopropyl group or the 1-butyl
substituent resulted in
compounds with overall improved
activity against gram-positive
bacteria.

7. • Modification of C-3 carboxylic acid
group leads to decrease in
antibacterial activity.
• However, replacement of C-3
carboxylic group with isothiazolo
group afforded most active isothiazolo
quinolone, which has been 4–10 times
greater in in vitro antibacterial
activity than ciprofloxacin.

8.  The C-4-oxo group of the quinolone
nucleus appears to be essential for
antibacterial activity.
 Replacement with 4-thioxo or sulphonyl
group leads to a loss of activity.
 The incorporation of a group at the C-
5 position has proven beneficial in
terms of antibacterial activity.

10. • A halogen (F or Cl) at the C-8
position improves oral
absorption.
• Linking of N-1 group to the
C-8 position with oxazine
ring leads to active ofloxacin.

11. NALIDIXIC ACID

12. NALIDIXIC ACID
The first quinolone to be marketed was nalidixic acid,
which has since been discontinued.
The 7-hydroxymethyl metabolite is significantly more
active than the parent compound.
Further metabolism of the active metabolite to inactive
glucuronide and 7-carboxylic acid metabolites also occurs.

13. Uses
•Nalidixic acid is
useful in the treatment
of urinary tract
infections in which
Gram-negative
bacteria predominate.

14. NORFLOXACIN

15. • The fluorine atom provides increased potency against Gram-positive
organisms, whereas the piperazine moiety improves antipseudomonal
activity.
• Norfloxacin possesses a broad spectrum of bactericidal action. It is highly
active with respect to most Gram-negative and a few Gram-positive
microorganisms.
 It is the first representative of a series of fluorinated quinolones
as well as the first drug of the quinolone derivatives used in
medicine that contains a piperazine substituent.

16. Uses
Norfloxacin is indicated for the treatment of urinary tract
infectionscaused by E. coli, K. pneumoniae, Enterobacter
cloacae, Proteus mirabilis.
 It is used for bacterial infections of the urinary tract, prostate
gland, gastrointestinal tract, gonorrhea, and traveler’s diarrhea.

17. ENOXACIN

18. ENOXACIN
• It only differs from norfloxacin in that
the carbon atom in position 8 of
norfloxacin is replaced with a nitrogen
atom, i.e. this drug belongs to the
napthiridine series and not the
quinolone series.
• Uses
• It is used primarily for the treatment of
urinary tract infections and sexually
transmitted diseases.

19. CIPROFLOXACIN

20. SYNTHESIS

21. USES
It is used for
infections of
the-
Urinary tract,
Respiratory
tract,
Biliary tract,
Infective-inflammatory diseases
of the abdominal cavity and
organs, bones, joints, and skin.

22. OFLOXACIN

23. OFLOXACIN
Ofloxacin has an asymmetric carbon atom in its structure, it
is obtained and supplied commercially as a racemate.
The 3S (–) isomer is substantially more active (8–125 times,
depending on the bacterial species) than the (3R+) isomer
and has been marketed as levofloxacin for the same
indications as the racemate.
Ofloxacin also possesses a broad spectrum of antimicrobial
action.
The oral bioavailability of ofloxacin is superior (95%–100%)
to that of ciprofloxacin, and metabolism is negligible
(approx.3%).

24. OFLOXACIN
• Uses
• It is used for infections of the respiratory
tract, ears, throat, nose, skin, soft tissue,
bones, joints, infective-inflammatory
diseases of the abdominal cavity organs
(kidneys, urinary tract), and organs of
the pelvis minor (genitalia), and for
gonorrhea.

25. LOMEFLOXACIN
• It is a difluorinated quinolone
with a longer elimination half-life
(7–8 hours) than other members
of its class.
• It is the only quinolone for which
once-daily oral dosing be
sufficient.
• It is a second generation
difluorinated quinolone, equal in
activity to ciprofloxacin but more
active against some gram-
negative bacteria and chlamydia.

26. LOMEFLOXACIN
Lomefloxacin reportedly causes the highest incidence of
phototoxicity (photosensitivity) of the currently available
quinolones.
Uses
Lomefloxacin also finds application in the treatment of chronic urinary tract
infections caused by Gram-negative bacilli

27. SPARFLOXACIN

28. SPARFLOXACIN
• It is second generation
difluorinated quinolone which
has enhanced activity against
gram- positive bacteria
USES
Sparfloxacin are used for the treatment of skin and soft tissue
infections, lower respiratory infections (including bronchitis
and bacterial pneumonias)

29. GATIFLOXACIN

30. GATIFLOXACIN
This is second generation FQ with
higher affinity for bacterial
topoisomerase IV was frequently
used for gram positive coccal
(mainly respiratory and ENT)
infections.

31. MOXIFLOXACIN
 It is the most potent FQ against M. tuberculosis.
 Bacterial topoisomerase IV is the major target of action.
Uses
Moxifloxacin is primarily
used for pneumonias,
bronchitis, sinusitis,
otitis media

32. FURAZOLIDONE
(3-[(5-
Nitrofurylidene)-
amino]-2-
oxazolidinone)
 Furazolidone, like the other nitrofuran derivatives.

33. FURAZOLIDONE
 In comparison with nitrofurazone and nitrofurantoin, furazolidone
is more active with respect to Gram-negative microorganisms, and
at the same time it is less toxic.
 Alcohol should be avoided when furazolidone is being used
because the drug can inhibit aldehyde dehydrogenase.
Uses
 Furazolidone has bactericidal activity against a relatively broad
range of intestinal pathogens, including S. aureus, E. coli,
Salmonella, Shigella, Proteus spp., Enterobacter, and Vibrio
cholerae.

34. NITROFURANTOIN (1-(5-
nitrofurfurylidenamino)-hydantoin)

35. NITROFURANTOIN
Nitrofurantoin is an
effective drug that acts
on a number of
Grampositive and Gram-
negative microorganisms.
Nitrofurantoin inhibits
DNA and RNA functions.

36. Synthesis

37. Uses
It is primarily used for
treating infectious
diseases of the urinary
tract (pyelitis,
pyelonephritis, cystitis,
urethritis).
It a widely used oral
antibacterial nitrofuran,
has been available since
World War II.
It also inhibits kidney stone
growth.

38. METHENAMINE
(hexamethylenetetramine)

39. METHENAMINE
Structurally it is a low molecular weight polymer of
ammonia and formaldehyde which reverts to its
components under mildly acid conditions.
 Formaldehyde is the active antimicrobial component.

40. Uses
• It is a drug that can be used for the disinfection of acidic urine.
• Methenamine can be used for recurrent urinary tract infections.
• It is also used internally as a urinary antiseptic for the
treatment of chronic urinary tract infections.
• The free base has practically no bacteriostatic power;
formaldehyde release at the lower pH of the kidney is
required.
• To optimize the antibacterial effect, an acidifying agent such
as sodium biphosphate or ammonium chloride generally
accompanies the administration of methenamine.

41. Thank You