MEDICINAL CHEMISTRY - ANTIBIOTICS - POLYPEPTIDE ANTIBIOTICS - B.pharmacy final year

1. POLYPEPTIDE ANTIBIOTICS
BY
KENCHA SWATHI
ASSISTANT PROFESSOR
DEPT OF MEDICINAL CHEMISTRY
ADITYA BIPER
BANGALORE

2. INTRODUCTION
Polypeptide antibiotics are a large diverse class of natural antibiotics containing only aminoacids
joined by amide bonds.
They are low molecular weight cationic polypeptides.
They are powerful bactericidal agents.
The peptide array may be linear or cyclic or various combinations thereof.
Eg: Gramicidin
Bacitracin
Polymyxin –B
Colistin

3. GRAMICIDIN
Structure:

4. BACITRACIN
Structure:

5. POLYMYXIN-B
Structure:

6. COLISTIN
Structure:

7. USES
It is used in the treatment of invasive aspergillosis in immunodeficiency patients.
To treat Histoplasmosis,Coccidioidomycoses,Meningeal coccidioidomycosis,Blastomycoses.
To treat fungal infections in lungs.
To treat GIT infections.
To treat skin,ear &eye infections.
To treat oropharyngeal decontamination or the suppression of intestinal flora in patient with high
risk of endogenous infections.
Used to treat infected wounds ,ulcers in combination with neomycin and polymixin

8. MECHANISM OF ACTION
• Polypeptide antibiotics are rapidly acting bactericidal agents.
• They shows detergent like action – high affinity for phospholipids.
• Orient of action between phospholipid and protein layers .
• This orientation causes membrane distortion or pseudophore formation.
• Pseudophore formation leads to leakage of ions ,amino acids and also inactivates the bacterial
endotoxins etc..,
• Polypeptides enters into the bacterial cell by showing synergism towards other protein molecules

9. MISCELLANEOUS ANTIBIOTICS
• The antibiotics which shows bactericidal property but not included under any class of antibiotics
like beta-lactam,aminoglycoside and tetracyclines are considered as miscellaneous category of
antibiotics.
• This class of drugs shows the antibiotic action by chance.
Eg: Chloramphenicol
Vancomycin
Novobiocin

10. CHLORAMPHENICOL
Structure:
Uses: 1.To treat typhoid fever,meningitis,rocky mountain spotted fever.
2.To treat Enteric fever
3.Chloramphenicol is alternative drug in place of cephalosporins.
4.To treat anaerobic infections and intraocular infections.

11. VANCOMYCIN
Structure:
Uses: 1.To treat serious gram +ve infections in β-lactam allergic patients.
2.To treat infections caused by multidrug resistant bacteria.
3.To treat endocarditis and infectious colitis.
4.To treat staphylococcal infections and pneumococci which are methicillin resistant

12. NOVOBIOCIN
Structure:
Uses: 1.Novobiocin is used to treat gram positive bacterial infections.
2. Novobiocin is used to differentiate coagulase negative staphylococci.
3.To check the resistant and sensitive bacteria.

13. MECHANISM OF ACTION
• Novobiocin inhibits bacterial DNA synthesis by targeting the enzymes like DNA gyrase,
DNA topoisomerase IV .
• Chloramphenicol is a bacteriostatic drug by inhibiting protein synthesis.It prevents protein chain
elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome .It specifically
binds to the 50s ribosomal subunit and prevents the peptide bond formation.
• Vancomycin inhibits cell wall synthesis by binding with the terminal alanine group of peptide
chain which further inhibits transpeptidase enzyme.This step prevents further elongation and
cross linking of the peptidoglycan layer of the cell wall.

15. REFERENCES
• Wilson and Gisvolds textbook of pharmaceutical and medicinal chemistry
• A textbook of medicinal chemistry by ashutoshkar
• GRAHAM PATRICK textbook of medicinal chemistry
• Textbook of medicinal chemistry by Ilango
• www.ncbi.nlm.nih.gov>pubmed