Unclassified:- These antibiotics have varied structures. Structure, Mechanism of Action of Chlorramphenicol, Rifampin...

1. UN-CLASSIFIED ANTIBIOTICS
• Mr. Hitesh Vishwanath Shahare
• Assistant Professor
• Dept. Ph.’ Chem.
• SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad

2. • Learners will be able to know;
2
1. SAR & MOA of Chloramphenicol
2. SAR & MOA of Rifampicin
3. MOA of Mupirocin
4. MOA of Linezolid
4
3
2
1

3. CHLORAMPHENICOL
• Obtained from Streptomyces venezuelae.
• Broad spectrum antibiotic, like Tetracyclines.
• Available as palmitate and succinate salt.
O
H
N
Cl
Cl
N
O
O
OH
OH
Chloramphenicol
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide
3

4. SAR
1. Replacement of the nitro group by other substituents leads to reduction in
activity
2. Shifting of nitro group from the Para position also reduces the
antibacterial activity
3. Replacement of phenyl group by the alicyclic moieties results in less
potent compounds
Part I: SAR of p-Nitro phenyl group
4

5. 1. Other dihaloderivatives of the side chain are less potent though major
activities are retained
2. While in case of trihalo derivatives (2-NHCOCF3) would be about 1.7 times
as active as chloramphenicol
SAR
Part II: SAR of Dichloroacetamido side chain
5

6. 1. The primary alcoholic group on C-1 atom if modified, results in a decrease in
activity hence the alcoholic group seems to be essential for activity.
2. Four stereoisomers of chloramphenicol, the antibacterial activity resides in
only D-threo compound.
6
Part III: SARof 1, 3-propanediol

7. Chloramphenicol
reversibly binds to 50S
subunit 50S
30S
70S
P A
MOA
Chloramphenicol
A U G
Inhibit peptide bond formation for
upcoming amino acids
(Polypeptide chain elongation)
Inhibit Peptidyl
Transferase
Inhibit Protein Synthesis
A U G

8. Clinical Uses
8

9. Adverse Effects
9
• Bone marrow Depression:Agranulocytosis, thrombocytopenia
• Hypersensitivity reactions: Rashes, fever
• Gray Baby Syndrome: cyanosis, vomiting, green stools,

10. 10

11. • The rifampin is a group of structurally similar, complex macrocyclic antibiotics
obtained from Streptomyces mediterrani.
• They belong to ansamycin class which consist of rifamycin A, B, C, D and E.
• Broad spectrum antibiotic.
• It can penetrate well cerebrospinal fluid and thus is used in the treatment of
tuberculous meningitis. It is also used to treat leprosy.
• SE: Hepatotoxicity
RIFAMPIN
11

12. SAR
• Aliphatic modifications do not help to retain the activity.
• In the naphthalene ring position-3 and 4 are bioactive and gives compounds
with similar activity.
12

13. MOA
Inhibits DNA-dependent RNA polymerase of mycobacterium by
forming a stable drug enzyme complex
Leading to suppression of initiation of chain formation in RNA
synthesis
Bactericidal DNA-dependent
RNA polymerase
Double stranded DNA Single stranded mRNA
Rifampicin

14. MUPIROCIN
• It is isolated from Pseudomonas fluorescens.
• Systemic administration results in rapid hydrolysis by esterases to mionic
acid, which is inactive in-vivo because of its inability to penetrate bacteria.
• It is used in the treatment of topical infections.
• Resistance to antibiotic is due to poor cellular penetration of the antibiotic.
14

15. MECHANISM OF ACTION
• It specifically and reversibly binds with bacterial isoleucyl transfer-RNA
synthase to prevent the incorporation of isoleucine into bacterial proteins.
O CH3
H
O
O O
OH
OH
HO
H
H3C
OH
H
O
CH3
Mupirocin
15

16. LINEZOLID
• It is oxazolidinedione type broad spectrum antibiotic.
• It binds to 30S and 50S ribosomal subunits and prevents interaction between
the two subunits. It inhibits protein synthesis by preventing the formation of a
functional initiation complex.
• It is used in the treatment of skin, soft tissue infection and drug resistant gram
positive infections.
O N N
O
CH3
O
F O
Linezolid
16

17. 17
hvshahare@gmail.com
Thank You!