Explanation of quinolones and fluoroquinolones from medicinal chemistry -6th semester third year bpharm

1. Pune District Education Association’s
Shankarrao Ursal College Of Pharmaceutical Sciences &
Research Centre Kharadi, Pune
Seminar On
Quinolones
By
Ms. Sakshi Gadekar (Roll No :20)
Ms.Aishwarya Kshirsagar(Roll No:35)
Third Year B.Pharm (Sem VI)
Guided By :
Ghule Mam
Academic Year:2023-2024
1

2. 2
Introduction of Urinary tract anti- infective agents:
• A urinary tract infection (UTI) is an infection that affects part of the urinary tract.
• The urinary tract made up of kidneys, ureters, bladder, and urethra.
• UTI are caused by bacteria, but some are caused by fungi and in rare cases by viruses.
• UTI are more common in women than men (8:1).
• Urinary tract infection is known as lower UTI/bladder infection/ cystitis, when affect
the lower urinary tract i.e. the urethra and bladder part it is most common UTI.
• Where as kidney infection /pyelonephritis ,when it affects the upper urinary tract i.e.,
the ureters and kidneys.
• Upper UTI are rarer than lower UTI.
• But more severe and life threatening if bacteria move from the infected kidney into
blood and this condition is called urosepsis, can cause low blood pressure, even death.
• Lower UTI are usually treated with oral antibiotics; whereas, upper UTI are treated via
intravenous antibiotics.

3. 3
• UTI can be prevented by hydration ( eight glasses of water daily ) and don’t hold urine for long periods
of time.

4. 4
Symptoms of Urinary Tract Infection:
• Burning sensation and pain with urination.
• Increased frequency of urination without passing much urine or feeling
urinate despite having an empty bladder.
• Increased urgency of urination.
• Bloody urine or cloudy urine.
• Urine that has a strong odour.
• Pelvic pain in women and rectal pain in men.
Symptoms of a kidney infection include:
• Fever and flank pain usually in addition to the symptoms of a lower UTI.
Symptoms of an upper UTI include:
• Pain and tenderness in the upper back and sides, chills, fever, nausea and
vomiting.
Diagnosis:
• Based & in complicated cases a urine culture may be useful .
• The most common cause of infection is Escherichia coli (80-85%).

5. Definition of Quinolones
• The Quinolones are a family of synthetic, broad spectrum antibiotic with
bactericidal activity.
• The term quinolone refers to potent synthetic chemotherapeutic antibacterial
agent.
• It has bicyclic core structure related to the substance 4-quinolones.
• E.g. Nalidixic acid, ciprofloxacin, etc.
5

6. History Of Quinolones:
6
• A group of synthetic antibacterial agents mainly effective agenist G-
ve.
• Nalidixic acid first member introduced in1964 for urinary and GIT
infrction.
• It’s congeners Oxolinic acid and rosoxacin with more potency in
1970s.
• Second generation called flouroquinolones with extended spectrum
and systemic effects in 1980s.
• Since then many synthesized with useful spectrum.

7. 7
Chemistry of Quinolones:
• They are synthetic fluorinated analogs of Nalidixic acid .
• Quinoloes is a nitrogen- containing hetrocyclic compound
having a fused Six-membered ring .
• It’s Chemical formula C9H7NO and a molar mass of
145.16g. Mol-1.

8. Classification Of Quinolones
•Quinolones can be classified into
generation based on their antibacterical
spectra.
•The earlier –generation agents are, more
narrow –spectrum than the later ones.
8

9. 9
Quinolones
2nd Generation
e.g. Norfloxacin
Ofloxacin
Lomefloxacin
3rd Genreation
e.g. Levofloxacin
4th Generation
e.g. Gatifloxain
Moxifloxacin
1St Generation
e.g. Nalidixic
acid
Piromidic
acid

10. 10
Mechanism of action of Quinolones :
1.They block bacterial DNA synthesis by inhibiting bacterial topoisomerase II(DNA
gyrase)and topoisomerase IV.
2.Inhibition of DNA gyrase prevents the relaxation of positively suoercoiled DNA
that is required for normal transcription and replication.
3.Inhibiton of topoisomerase IV probably interferes with separation of replicated
chromosomal DNA into the respective daughter cell during cell division.

11. 11

12. 12
SAR Of Quinolones:

13. 13
• The carboxyl group at 3rd position is essential.
• Ketone group at 4th position is essential for antimicrobial
activity.
• Substitution at position 6 with a fluorine moiety markedly
increase antibacterial activity against G+Ve,G-Ve ,
Mycoplasma and chlamydia….
• Addition of a piperazine ring at position 7 on
fluoroquinolones increases tissue and bacterial penetration and
improves spectrum of activity to include Pseudomonas.
• E.g. Ciprofloxacin, Enrofloxacin

14. 14
Drug Profile of Quinolones :
 .Nalidixic Acid:
 Nalidixic acid is the first of the synthetic quinolones antibiotics.
 It is chemically 1-ethyl -7-methyl-4-oxo-1,8-napthyridine-3-carboxylic acid.
 It’s ring structure is a 1,8-napthyridine nucleus that contains two nitrogen atoms.
 It is effective primarily against Gram-negative bacteria,with minor anti-Gram –positive activity
 In lower concentrations, bacteriostatic manner, that inhibits growth & reproduction.
 In higher concentration , it is bactericidal, it kills bacteria.
 Nalidixic acid related antibiotics inhibit a subunit of DNA gyrase & include formation of cleavage which are
essential for DNA replication in bacteria.

15. 15
Uses
• Nalidixic acid is used for treating urinary tract infection caused by certain bacteria.
• It is used for treating urinary tract infection , e.g. by Escherichia coli, proteus, shigella, Enterobacter, &
klebsiella.
2. Ciprofloxain
 Ciprofloaxin is a broad- spectrum antibiotic of the fluoroquinolone class
 It is chemically,1- cyclopropyl-6-fluoro- 4- oxo -7-piperazin-1-yl quinoline -3- carboxylic acid.
 It inhibits bacterial DNA gyrase, an enzyme essential for DNA replicaton & inhibits topoisomeraseIV enzyme
 It is active against some Gram-positive and many Gram- negative bacteria.
 It has a role as an anti-infective agent, a topoisomerases-IV inhibitor, an anti bacterial drug, a DNA synthesis
inhibitor, an antimicrobial agent, an environmental contaminant a xenobiotic.
Uses:
 Is widely used in the therapy of mild –to- moderate urinary and respiratory tract infection caused by susceptible
organisms.
 It is also used to treat a wide variety of other infections, including infections of bones and jonits, gastroenteritis,
malignant otitis externa, cellulitis, prostatitis and anthrax.

16. 16
3. Lomefloxacin:
 Lomenfloxacin is a synthetic broad- spectrum fluoroquinolones with antibacterial activity.
 It is chemically , 1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1—yl)-4-oxoquinoline-3-caeboxylic acid.
 It inhibits DNA gyrase, a type –II topoisomerase involved in the induction or relaxation of supercolling during
DNA repliction.
 This inhibition leads to a decrease in DNA synthesis during bacterial replication , resulting in cell growth
inhibition and eventually cell lysis.
Uses:
 Lomefloxacin is used to used to treat bacterial infections including bronchitis & urinary tract infection.
 It is also used to prevent urinary tract infections prior to surgery.
 It has a role as an antimicrobial agent, a photosensitizing agent and antitubercular agent.

17. 17
REFERENCES:
 Essentials of Medical Phramacology by K D Tripathi, 8th edition, Page No, 759-765.
 Lippincott Illustrated Reviews Pharmacology by Karan Whalen, 5th edition , Page
No, 409-413.
 Rang & Dale’s Pharmacology, 9th edition, Page No, 672.
 Dr. SANJAY G. WALODE, Dr. CHANDAN R.S., Dr. (Mrs.) ALPANA J. ASNANI
Textbook of medicinal chemistry , Nirali prakashan , second edition, Page No-6.1 to
6.9
 Andersson MI, MacGowan AP (May 2003). Development of the quinolones.” The
Journal of Antimicrobial Chemotherapy. 51 (Suppl S1): 1-11. doi: 10.
1093/jac/dkg212. PMLD 12702698.

18. 18