ppt of lincomycins

1. 
 Name:- Ankit V. Deore
 Std :- Final Year B Pharmacy
 Sub:- Medicinal Chemistry-III
 Roll No. :- 12
 Topic :- Linomycins (lincosamides)
 Guide by:- Mr. Dabhade Sir
Medicinal Chemistry-III

2. 
 Introduction
 Classification
 Structures
 Chemical name
 IUPAC name
 Mechanism of action
 Structural activity
 Toxicity
 Uses
INDEX

3. 
 Inroduction-
 Lincomycin is a lincosamide antibiotic that comes
from the actinomycete Streptomyces lincolnensis. A
related compound, clindamycin, is derived from
lincomycin by using thionyl chloride to replace the 7-
hydroxy group with a chlorine atom with inversion
of chirality. It was released for medical use in
September 1964
Lincomycin

4. 
 Lincomycin
 Clindamycin
Classification-

5. 
 An antibiotic produced by Streptomyces lincolnensis
var. lincolnensis. It has been used in the treatment of
staphylococcal, streptococcal, and Bacteroides
fragilis infections.
 Chemical Formula- C18H34N2O6S
1)Lincomycin

6. 
 Structure –

7. 
 IUPAC-
 (2S,4R)-N-[(1R,2R)-2-hydroxy-1-[(2R,3R,4S,5R,6R)-
3,4,5-trihydroxy-6-(methylsulfanyl)oxan-2-
yl]propyl]-1-methyl-4-propylpyrrolidine-2-
carboximidic acid

8. 
 Mechanism of action-
 Lincomycin inhibits protein synthesis in susceptible
bacteria by binding to the 50 S subunits of bacterial
ribosomes and preventing peptide bond formation
upon transcription. It is usually considered
bacteriostatic, but may be bactericidal in high
concentrations or when used against highly
susceptible organisms.

9. 
 Clindamycin is a semisynthetic lincosamide
antibiotic that has largely replaced lincomycin due to
an improved side effect profile. Clindamycin inhibits
bacterial protein synthesis by binding to bacterial 50S
ribosomal subunits. It may be bacteriostatic or
bactericidal depending on the organism and drug
concentration.
2) Clindamycin

10. 
 Structure –

11. 
 Chemical Formula-C18H33ClN2O5S
 IUPAC Name-(2S,4R)-N-[(1S,2S)-2-chloro-1-
[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-
(methylsulfanyl)oxan-2-yl]propyl]-1-methyl-4-
propylpyrrolidine-2-carboximidic acid

12. 
 Mechanism of action-Systemic/vaginal clindamycin
inhibits protein synthesis of bacteria by binding to
the 50S ribosomal subunits of the bacteria.
Specifically, it binds primarily to the 23s RNA
subunit. Topical clindamycin reduces free fatty acid
concentrations on the skin and suppresses the
growth of Propionibacterium acnes
(Corynebacterium acnes) , an anaerobe found in
sebaceous glands and follicles.

13. 
 Toxicity-Adverse effects include nausea (may be dose-
limiting), diarrhea, pseudomembranous colitis, allergic
reactions, hepatoxicity, transient neutropenia and
eosinophilia and agranulocytosis. Pseudomembranous
colitis occurs in 0.01 - 10% of patients and occurs more
commonly than with other antibiotics. Use of the topical
formulation of clindamycin results in absorption of the
antibiotic from the skin surface. Diarrhea, bloody
diarrhea, and colitis (including pseudomembranous
colitis) have been reported with the use of topical and
systemic clindamycin.
Toxicity

14. 
 SAR--Lincomycin is a 6-amino, 6-deoxy-octopyraninose
with strong antibiotic activity. To maintain or enhance
this activity, one must have the configuration of the first
five asymmetric carbons of the sugar residue with the
thioglycolic moiety in the alpha-position. The nitrogen on
carbon 6 with the R configuration is also a prerequisite for
the activity. Substitutions at the level of C-7 as well as the
pyrolidine moiety can dramatically enhance this activity.
The streptogramin group is composed of a wide variety
of structures which can be classified into two subgroups.
Group A or M is composed of polyunsaturated cyclic
peptolides, e.g. pristinamycin IIA; group B or S is
composed of cyclic hexadepsipeptides.
Structural activity

15. 
 Separately, these molecules have a bacteriostatic activity
on Gram-positive organisms, whereas in association they
exhibit a strong and synergistic bactericidal effect. The 13-
OH function of PIIA is essential for antibiotic activity to
occur whereas the 15-carbonyl function can be reduced
with the retention of the biological properties of the drug.
The carbonyl function of PIA can be reduced and the
pipecolic moiety can be replaced by other groups without
a dramatic influence on the antibiotic activity. The
macrocyclic lactone ring is necessary for antibiotic
activity.

16. 
 Although similar in structure, antibacterial
spectrum, and mechanism of action to macrolides,
lincomycin is also effective against other organisms
including actinomycetes and some species of
Mycoplasma and Plasmodium.[citation needed]
 However, because of its adverse effects and toxicity,
it is rarely used today and reserved for patients
allergic to penicillin or where bacteria have
developed resistance.
Uses-

17. 
Prepared by-Ankit V. Deore