The document discusses several classes of antibiotics including beta-lactam antibiotics such as penicillins and cephalosporins, which work by inhibiting bacterial cell wall synthesis, macrolides which inhibit bacterial protein synthesis, and carbapenems which are resistant to beta-lactamases and bind to penicillin-binding proteins. It provides details on the mechanism of action, sources, classification, structure, and examples of drugs for each class.
1. Antibiotics
(Beta lactam & Macrolide )
By
Kamble Mangal Y.
M pharm First Year
Pharmaceutical Chemistry Department
Guided by-Dr. Revan Karodi
Dr. D.Y. Patil College Of Pharmacy Akurdi ,Pune.
3. ANTIBIOTICS –
Antibiotic are chemical substance produced by
microorganism that inhibit the growth or kill other
microorganism.
Sources
1. Natural
a. Fungi – penicillin, griseofulvin
b. Bacteria – Bacillus sp. (polymixin, bacitracin) ;
Actinomycetes(tetracycline, chloramphenicol,
streptomycin)
2. Synthetic
4. ANTIBIOTICS – Classification
I. According to antimicrobial activity
1. Bactericidal
2. Bacteriostatic
II. According to bacterial spectrum of activity
1. Narrow spectrum
2. Broad spectrum
III. According to absorbability from the site of
administration to attain significant concentration for the treatment
of systemic infection
1. Locally acting
2. Systemic
5. IV. According to mechanism of action
1. Inhibit bacterial cell wall synthesis
2. Alter the function and permeability of the cell membrane
3. Inhibit protein synthesis (translation and transcription)
4. Inhibit nucleic acid synthesis
7. β-Lactam antibiotics
• The name “Lactam” is given to cyclic amides
and is analogous to the name “Lactone” which is
given to cyclic ester .
• Antibiotics that contains the β-lactam (a four
membered cyclic amide) ring structure constitute
the dominant class of agent currently employed
for the chemotherapy of bacterial
infections.
• β-lactam are the most widely used group of
antibiotics available.
8. β- Lactam Antibiotics
β-lactam antibiotics, inhibit bacterial growth by interfering
with bacterial cell wall synthesis.
The β-lactam antibiotics may be further subdivided
into four categories, namely:
Penicillin
Cephalosporin
Carbapenem
Monobactam
9. Cephalosporins
• Cephalosporins were discovered shortly after penicillin
entered into widespread product, but not developed till the
1960’s.
• Cephalosporins are similar to penicillins but have a 6
member dihydrothiazine ring instead of a 5 member
thiazolidine ring.
• 7-aminocephalosporanic acid (7-ACA) can be obtained
From Bacteria.
• They were isolated from cultures of Cephalosporium
acremonium by italian scientist Giuseppe Brotzu in 1945.
10.
11.
12. Mechanism of Action
• Cephalosporins exert bactericidal effect in manner similar
to that of Penicillin.
• Binding to specific PBPS.
• Inhibition of cell wall synthesis by inhibiting
transpeptidation of Peptidoglycan.
• Bind to different protein than those which bind penicillin
PBP-1&PBP-3.
13.
14. Chemistry
• The nucleus of Cephalosporins, 7-Amino cephalosporanic acid
bears a close resemblance to 6-aminopencillanic acid.
• The core of the basic cephalosporin molecule consists of a two
ring system which includes a β-lactam ring condensed with
dihydrothiazine ring.
• The core itself can also be referred to as 7-Amino
cephalosporanic acid which can be derived by hydrolysis from
the natural compound Cephalosporin C.
17. The agents included in this group have good activity against
gram-positive cocci, such as pneumococci, streptococci and
staphylococci but not active against methicillin resistant
strains of staphylococci, and relatively modest activity
against gram-negative microorganisms (E.Coli and
Klebsiella pnumoniae).
18. cephachlor cephamycin
Second Generation Cephalosporins
They have a greater gram-negative spectrum while retaining
some activity against gram-positive bacteria.
They are also more resistant to β-lactamase.
No BBB Penetration.
20. Third-generation drugs exhibit the lest activity against gram-
positive bacteria, but most potent activity against gram-
negative bacteria :
(a) Extended antibacterial spectrum, include Pseud.
aeruginosa;
(b) Less activity on gram-positive bacteria than first and
second generation;
(c) Most active on gram-negative bacteria;
(d) High stability with β-lactamase;
(e) Easy penetrate to different tissues, and then have broad
distribution;
21. cefepime cefpirome
fourth Generation Cephalosporins
• Zwitterionic compounds.
• Good affinity for the transpeptidase
enzyme.
• Low affinity for some β-lactamases.
• Cross BBB and effective in meningitis.
24. Carbapenem
• Introduction
Carbapenems are a class of β-lactam antibiotics with a broad
spectrum of antibacterial activity.
They have a structure that renders them highly resistant to most
β-lactamases.
Carbapenem antibiotics were originally developed from the
carbapenem thienamycin, a naturally derived product of
Streptomyces cattleya
Examples: Imipenem, Meropenem, Ertapenem, Doripenem
25. Mechanism of action
Closely related to penicillins, carbapenems are
bactericidal beta-lactam antibiotics that bind to
penicillin-binding proteins (PBPs).
By binding and inactivating these
proteins, carbapenems inhibit the synthesis of the
bacterial cell wall, which leads to cell death.
26.
27. IMIPENEM:
Imipenem has a wide spectrum with
good activity many gram negative rods
including P. aeruginosa, gram positive organisms and
anaerobes.
Imipenem is inactivated by dehydropeptidases in renal
tubules, result in low urinary concentrations.
28. Meropenem:
This is newer carbapenem is not hydrolysed by renal
peptidase.
It is active against both Gram +ve & Gram –ve bacteria,
aerobes as well as anaerobes.
29. Ertapenem:
It is new carbapenem with antibacterial activity similar
to other member but less broad spectrum.
It is highly active against E. Coli, H. influenzae, K.
pneumoniae and many Anaerobes.
30. Doripenem:
This later introduced carbapenem has
antimicrobial activity similar to meropenem, but
more active against some resistant pseudomonas.
31. Macrolides
The macrolides are a group of antibiotics produced by
various strains of Streptomyces and having a macrolide
ring structure linked to one or more sugars. They act by
inhibiting protein synthesis, specifically by blocking the
50S ribosomal subunit. They are broad spectrum
antibiotics.
Examples: Erythromycin, Azithromycin, Clarithromycin,
Roxithromycin etc……………
32. Mechanism of Action
Macrolide is a protein synthesis inhibitor
Macrolide bind to 50S ribosomal subunit
Inhibit polypeptide chain elongation &
protein synthesis inhibition
Result in inhibition of growth &
multiplication
33.
34.
35. SOURCE:
These Are Produced By Streptomyces species.
CHEMISTRY:
• A macro cyclic lactone, usually having 12 to 17 atoms.
• A ketone group.
• One or two amino sugars linked to the nucleus.
• A neutral sugar linked either to amino sugar or to lactone
ring.
• The presence of the dimethyl amino moiety on the sugar
residue, which explains the basicity of these compounds
and consequently formation salts.
36.
37. SAR
1.As macrolide are unstable in acidic pH.
2.The addition of hydroxylamine to the ketone to form
oxime
e.g. roxithromycin.
3.Alteration of c-6 hydroxyl group: nucleophilic
functionality which initiates erythromycin degradation.
4.The azalides (azithromycin)are semi- synthetic 15 –
membered congeners in which a nitrogen atom has
been introduced to expand a 14-membered precursor-
leads to an extended spectrum of action.
39. Erythromycin isolated from streptomyces erytherus in
1952.it has been widely employed & alternative with
Penicillin.
It shows bacteriostatic at low conc.& cidal at high
conc.
It inhibit protein synthesis by combine with 50S
ribosome& interfere in translocation.
Physical properties:
• Yellow to white crystalline powder.
• Soluble in alcohol, slightly soluble in water.
• Stable at neutral pH.
41. • Nitrogen containing15 membered lacton ring
macrolide(azalide).
• Stable under acidic condition, it does not form
cyclic ketal.
• Strongest activity against mycoplasma pneumoniae.
• More effective on Gram negative bacteria.
• Well tolerated.
properties
43. Azithromycin is more active other macrolide against H.
influenza, but less active against gram +ve cocci.
Advantages
• Cannot undergo cyclic ketal formation, so doesn’t
cause cramp in GI
• Higher blood concentrations.
• More lipophilic.
• Lower doses with less intervals.
Uses:
• Atypical mycobacterial infection
• Resistant leprosy
• Toxoplasmosis
• H.Pylori induced peptic ulcers
45. properties:
Semi-synthetic 14–membered ring macrolide
Longer acting acid stable antibiotic whose
antimicrobial spectrum resemble closely with
erythromycin.
Uses:
• Active against both gram (+) & gram (-).
• Treatment of skin ,dental & genital infections.
• Treatment of upper & lower respiratory tract
infections.
46. Rreference
1) Essentials of MEDICAL PHARMACOLOGY; KD
Tripathi.
2) Foyle's Principle of MEDICINAL CHEMISTRY.
3) Cephalosporins & other β-Lactam Antibiotics, Cell Wall
Destructors,slide share presented by Faraza Javed
M phil Pharmacology.
