Introduction to Antibiotics,Classification,General Mechanism of action,Penicillin,Classification of Penicillin,Moa,Structure Activity Relationship,Uses

1. Prepared by –
Ms.S.P.Desai
Assistant Professor
ADCBP
Antibiotic

2. Antibiotics
Definition:
These are substances produced by the microorganisms,
which has the capacity of inhibiting the growth and
even of destroying other micro- organisms.

3. Antibiotics are defined as chemical substances or
compounds produced by various species of
microorganisms such as bacteria and fungi, which
in low concentrations destroy, kill or inhibit the
growth of other species of microorganisms.
” Greek words anti = against ; bios = life
Vuillemin to define antibiotics literally meaning
“against life”
In 1942 Waksman proposed the widely cited
definition that “an antibiotic is a substance
produced by microorganisms, which has the
capacity of inhibiting the growth and even of
destroying other microorganisms”.

4. The word antibiotic came from the word antibiosis a term
coined in 1889 by Louis Pasteur's pupil Paul Vuillemin
which means a process by which life could be used to
destroy life.
However, by acylating it with various acid derivatives,
more than 50,000 semisynthetic penicillins have been
made, of which less than 30 are currently used in
medicine.

5. Characteristics of Antibiotics
• It should have a wide spectrum of activity with the
ability to destroy or inhibit many different species of
pathogenic organisms.
• It should be eliminated completely from the body.
• It should not produce adverse and side effects.
• It should antagonizes the growth or survival of one
or more species of micro- organisms.
• It should be highly effective in low concentrations.
• It should be nonallergenic to the host.
• It should be chemically-stable (have a long shelf-life).

6. • It is a product of metabolism (although it may be
duplicated or even have been anticipated by
chemical synthesis).
• It should not eliminate the normal flora of the host.
• It should be able to reach the part of the human
body where the infection is occurring.
• It should be inexpensive and easy to produce.

7. Classification of Antibiotics
According to Chemical Structure:
1.β-lactamase atibiotics: Penicillins, Cephalosporins, Monobactams,
Carbapenems.
2. β-lactamase inhibitors : Clavulanic acid, Sulbactam,Tazobactum.
3. Tetracyclins: Oxytetracycline, Doxycycline, etc.
4. Nitrobenzene derivative: Chloramphenicol.
5. Aminoglycosides: Streptomycin, Gentamicin, Amikacin, Neomycin, etc.
6.Macrolide antibiotics: Erythromycin, Roxithromycin, Clarithromycin,
Azithromycin.
7. Lincosamide antibiotics: Lincomycin, Clindamycin.
8.Polypeptide antibiotics: Polymyxin-B, Colistin, Bacitracin, Tyrothricin.

8. According to Mode of action

9. General Mechanism of action of Antibiotics

10. Four groups Beta-lactam antibiotics
• Beta-lactam antibiotics will be examined in four groups,
including penicllins, cephalosporins, monobactams, and
carbapenems.
• The beta-lactam ring is joined to a five-membered thiazolidine
ring in penicillin,
• Six-membered dihydrothiazine ring in cephalosporins.

11. • In carbapenems, the beta-lactam ring is also joined to a five-
membered ring, although it is carbocyclic.
Monobactams have a monocyclic betalactam structure, and
the side sulfo-group is joined to a nitrogen atom.
All of these contain a four-membered beta-lactam ring, which
is necessary for exhibiting antibacterial activity.

12. Penicillin
• Penicillin was discovered in 1928 by Alexander Fleming,
who noticed that one of his experimental cultures of
staphylococcus was contaminated with mold, which
caused the bacteria to lyse. Since mold belonged to the
family Penicillium, he named the antibacterial substance
penicillin.
• About a decade later, a group of researchers at Oxford
University isolated a crude substance made up of a few
lowmolecular substances, which were penicillins (F, G, K,
O, V, X).
• Penicillin is a secondary metabolite produced by certain
bacteria, which is used an antibiotic .

13. Structure of Penicillin
• The penicillin nucleus consist of fused thiazolidine
and β-lactum ring.to which side chains are attached
through an amide linkage.
• Penicillins are very reactive due to strained amide
bond in the fused β-lactum of the nucleus.

17. SAR of Penicillin
1) Penicillins are a group of antibiotics that contain 6-amino
penicillanic acid side chain attached to the 6-amino group essential for
activity.
2) The penicillin nucleus is the chief structural requirement for
biological activity.
3) The side chain structure determines the many of the antibacterial
and pharmacological characteristics.
4) The strained β-lactum ring is essential.
5) The penicillin contains β-lactum ring is fused with thiazolidine ring.
6) The free carboxylic acid is essential.the carbolated ion is binds to the
charged ammonium ion of lysine residue in the binding site.
7) The bicyclic system is important.The greater the strain,the greater
the activity.
8) The acyl amino side chain is essential.

18. Con…
9) The sulfur is usual but non essential.
10) The cis-streochemistry of bicyclic ring with respect to the acyl
amino side chain is important.
11) Oxidation of sulphur to a sulfone or sulfoxide will decrease the
activity.
12) The methyl group s at position 2 are essential.
13) β-lactum carbonyl group at position 7 is must.
14) The carboxylic acid is changed to an alcohol and ester activity is
decreased.
15) N at position 4 is must for antibacterial activity.
16) Placing the electron withdrawing group in the side chain which
could draw electrons away from the carbonyl oxygen and reduce
the tendency to act as a nucleophile and allows a greater stability
and oral bioavailability eg.Penicillin V , Ampicillin.
17) By placing bulky groups on the side chain it prevent the penicillin
from entering the penicillinase.

19. Con…
18) Broad spectrum activity is associated with the presence of α-hydrophilic
group on the acyl side chain of penicillin.
19) Enhancement of gram-ve activity is increased hydrophilic group ,attached
to the carbon α,to the carbonyl group on the side chain. These penicillins are
having useful activity against both remove ad gram–ve.
20) The spectrum of activity was further extended with introducing strong
acidic group is attached to the carbon α- to the carbonyl group on the side
chain.
21) Urido penicillins have a urea functional group at α-position. In fact they
are more active than the carboxy penicillins against streptococci and
haemophilus species. Presence of urea group gives improved penetration in
to gram–ve species. eg. Azocillin, Mezlocillin, Piperacillin.

20. Mechanism of action of Penicillin
• The primary mechanism of the action of β-lactum antibiotics is the
inhibition of synthesis of cell wall of bacteria.which causes them to
quickly die.
• Penicillins like all beta-lactum antibiotics,inhibit bacterial growth by
interfering with the transpeptidation reaction of bacterial cell wall
synthesis.
• The cell wall is composed of a complex cross-linked polymer of
polysaccharides and polypeptides called peptidoglycan.
• The polysaccharides contains alternating amino sugars.N-
acetylglucosamine and N-acetylmuramic acid.
• A five-amino-acid peptide is linked to the N-acetylmuramic acid
sugar.
• This peptide terminates in D-alanyl-D-alanine.

21. Con….
• Penicillin-binding protein removes the terminal alanine in the
process of forming a cross-link with anearby peptide.
• Beta-lactum antibiotics,structural analogs of the natural D-Ala-D-Ala
substrate covalently bind to the avtive site of PBPs. This inhibits the
transpeptidation reaction,halting peptidoglycan synthesis,and the
cell dies.
• The exact mechanism of cell death is not completely
understood,but autolysins and disruption of cell wall
morphogenesis are involved.
• Penicillins and cephalosporins kill bacterial cell only whwn theyare
actively growing and synthezing cell wall.

23. Uses of Penicillin
1) Drugs of the penicillin group are effective for infections
caused by Gram-positive bacteria,spirochaetae and other
pathogenic microorganisms.
2) Drugs of this group are effective with viruses,mycobacteria
tuberculosis,fungi and the majority of gram-negative
microorganisms
3) Benzylpenicillin is the drug of choice for infections caused
by sensitive organisms.This includes streptococci
infections,gonococci and meningococci that do not produce β
–lactum anaerobes.
Benzylpenicillin is used for croupous and focal pneumonia
,skin infections,soft tissue and mucous
membranes,periotonitis,cystisis.