Antibiotics.pptx

ANTIBIOTICS
DR. MANJOOR AHAMAD SYED,
M.Pharm,Ph.D
Associate. Professor
Department of Medicinal Chemistry,
College of Public Health and Medical Sciences,
Mettu University, Mettu
Post Box No-318
Ethiopia.

ANTIBIOTICS
Antibiotics are chemical substance or compounds produce 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.

CLASSIFICATION
Antibiotics are classified in many ways based on chemical structure, they are
1. β – Lactam Antibiotics
a. Penicillin’s : E.g. Penicillin, Ampicillin, Amoxycillin
b. Cephalosporins: E.g. Cephalexin, Cefixime
c. β – Lactamase inhibitors: E.g. Clavulanic acid, Sulbactam, Tazobactam, Thienamycin
d. Monobactams: E.g. Aztreonam, Tigemonam
2. Aminoglycosides
E.g. Amikacin, Streptomycin, Kanamycin, Gentamycin
3. Tetracyclines
E.g. Chlortetracycline, Oxytetracycline, Doxycycline
4. Macrolides
E.g. Erythromycin, Azithrocin

CLASSIFICATION
5. Lincomycin’s
E.g. Lincomycin, Clindamycin
6. Polypeptides
E.g. Gramicidin, Bacitracin, Polymyxin B
7. Miscellaneous
E.g. Chloramphenicol and Vancomycin

Antibiotics Mechanism of Action
• InhibitorsofDNA synthesis
• Inhibitorsofbacterialprotein synthesis
• Inhibitorsofbacterialcellwall synthesis
• Interferencewith metabolism
• Impairmentof nucleic acids

β – Lactam Antibiotics
• Penicillin, cephalosporins, monobactams,
carbapenems, and β- lactamase inhibitors
• Four-membered lactam ring.
• Thiazolidine or Dihydrothiazine (A) ring is attached to a
β-lactam ring (B) that carries a secondary amino group
(RNH–)

How do they work?
1. The β-lactam binds to Penicillin Binding Protein (PBP)
2. PBP is unable to crosslink peptidoglycan chains
3. The bacteria is unable to synthesize a stable cell wall
4. The bacteria is lysed

MECHANISM OF β-LACTAM DRUGS
The hydroxyl attacks the
amide and forms a
tetrahedral intermediate.
S
N
CH3
R
CH3
O
COOH
OH
SER
H
The tetrahedral intermediate
collapses, the amide bond is broken,
and the nitrogen is reduced.
S
N
CH3
R
CH3
O
COOH
SER
O
- H

Mechanism of β-Lactam Drugs
The PBP is now covalently bound by the drug and
cannot perform the cross linking action.
S
N
H
CH3
R
CH3
COOH
O
O
SER

STEREO CHEMISTRY
 The penicillin molecule contains three chiral carbon atoms at C-3, C-5, and C-6.
 All natural and synthetic penicillins have the same absolute configuration about
these three centres.
 The 6th carbon atom bearing the acyl amino group has the L-configuration, where
as the carbon to which the carboxyl group was attached has the D-configuration.
 Thus the acyl amino group and carboxyl group are trans to each other, with the
former α and later β orientation relative to penam ring.
 The absolute stereochemistry of the penicillins was designated as 3S: 5R: 6R.
 The atoms composing the 6-aminopenicillillanic acid are biosynthetically derived
from two amino acids are L-cysteine and D-valine.

 Penicillins inhibit a bacterial enzyme called the transpeptidase enzyme which is
involved in the synthesis of the bacterial cell wall.
 The β-lactam ring is involved in the mechanism of inhibition.
 Penicillin becomes covalently linked to the enzyme’s active site leading to irreversible
inhibition.
N
S Me
Me
H
N
H H
CO2H
O
C
O
R
Nu
Enz
C
H
N
C
CO2H
H
H
Me
Me
S
HN
O
R
O
Nu-Enz
-H
N
S Me
Me
H
N
H H
CO2H
O
C
H
Enz-Nu
O
R
Mechanism of action
 Covalent bond formed to transpeptidase enzyme
 Irreversible inhibition

Mechanism of action - bacterial cell wall synthesis
 Penicillins inhibit a bacterial enzyme called the transpeptidase enzyme which is
involved in the synthesis peptidoglycan layer containing NAG & NAM connected by
penicillin binding proteins (PBP) of the bacterial cell wall.

Mechanism of action - bacterial cell wall synthesis

Nomenclature
Nomenclature of penicillins is done with different systems as
following:
i. Chemical Abstract System (CAS):
ii. United State Pharmacopoeia (USP system):
Chemical Abstract System:
According to CAS penicillins are numbered starting from “S” atom.
Hence sulfur atom is assigned the 1st position and “N” atom is
assigned number 4th position and is called 6-acylamino-2,2-
dimethyl-3-carboxylic acid.
S
N
CH3
CH3
COOH
NH
C
R
O
O
1
2
3
4
5
6
7
United State Pharmacopoeia system:
This system of naming penicillins is the reverse of CA
system. According to this system the nitrogen atom is
given the 1st position and “S” atom is assigned the 4th
position and is called 4-thia-1-azabicyclo heptone.
S
N
CH3
CH3
COOH
NH
C
R
O
O
1 2
3
4
5
6
7

CHEMICAL DEGRADATION OF PENICILLINS
S
N
CH3
CH3
COOH
NH
C
R
O
O
penicillin
CH3OH NaOH
alakaline pH S
N
H
COOH
CH3
CH3
COOH
NH
C
R
O
penicilloic acid
- CO 2
decarboxylation
S
N
H
CH2 CH3
CH3
COOH
NH
C
R
O
penilloic acid
acidic pH
HgCl 2/H2O
S
H
N
H2
CH3
CH3
COOH
+
CHO
CH2
NH
C
R
O
penicillamine
penillo aldehyde
S
N
H
H3COOC
CH3
CH3
COOH
NH
C
R
O
Methyl penicilloate
Aq. HgCl 2
S
H
N
H2
CH3
CH3
COOH
+
CHO
CH
NH
C
R
O
COOCH 3
penicillamine
methyl penaldate
acidic pH / dil. acid
H / HgCl 2
S
N
CH3
CH3
COOH
N
HOOC
R
penillic acid
amidase
S
N
CH3
CH3
COOH
N
H2
O 6-APA

Hydrolysis of penicillins by hot and cold dilute mineral acids
S
N
CH3
CH3
COOH
NH
C
R
O
O
S
N
H
CH3
CH3
COOH
O
N
O
R
pseudopenicillin
penicillin
acidic pH
H
+
S
H
N
H
CH3
CH3
COOH
O
N
O
R
penicillenic acid
hot dil. acid
H
+
N
N
S
R
HOOC
CH3
CH3
COOH
penillic acid
H2O
HgCl2
S
H
N
H2
CH3
CH3
COOH
+
CH2
COOH
NH
C
R
O
penaldic acid
penicillamine
NaOH
alakaline pH S
N
H
COOH
CH3
CH3
COOH
NH
C
R
O
penicilloic acid
- CO2
decarboxylation
S
N
H
CH2 CH3
CH3
COOH
NH
C
R
O
penilloic acid
acidic pH
HgCl2/H2O
S
H
N
H2
CH3
CH3
COOH
+
CHO
CH2
NH
C
R
O
penicillamine
penillo aldehyde
neutral pH

Hydrolysis of penicillins by methanolysis followed by aqueous mercuric chloride
Degradation of penicillins with methyl alcohol results in formation of an ester that is methyl
penicilloate, further treatment with Aq. HgCl2 yields methyl penaldate and penicillamine.
S
N
CH3
CH3
COOH
NH
C
R
O
O
penicillin
CH3OH S
N
H
H3COOC
CH3
CH3
COOH
NH
C
R
O
Methyl penicilloate
Aq. HgCl 2
S
H
N
H2
CH3
CH3
COOH
+
CHO
CH
NH
C
R
O
COOCH 3
penicillamine
methyl penaldate

S
N
CH3
CH3
COOH
NH
C
R
O
O
penicillin
-lactamase S
N
H
CH3
CH3
COOH
NH
C
R
O
HOOC O
H2O (hydrolysis)
or penicillinase
S
N
H
HOOC
CH3
CH3
COOH
NH
C
R
O
penicilloic acid
+
CH2OH - - lactamase
ENZYMATIC HYDROLYSIS WITH PENICILLINASE (OR) β-LACTAMASE

Generic name R - group
Penicillin - G
Penicillin - V
Penicillin – X
Methicillin
CH2
O CH2
CH2
O
H
OCH 3
OCH 3
S
N
CH3
CH3
COOH
NH
C
R
O
O

Nafcillin
Oxacillin
Cloxacillin
Dicloxacillin
OC2H5
N
O CH3
N
O CH3
Cl
N
O CH3
Cl
Cl
S
N
CH3
CH3
COOH
NH
C
R
O
O

Carbenicillin
Ticarcillin
CH
COOH
S
CH
HOOC
S
N
CH3
CH3
COOH
NH
C
R
O
O
Ampicillin
Amoxicillin
CH
NH2
CH
O
H
NH2
S
N
CH3
CH3
COOH
NH
C
R
O
O

PENICILLIN G (Benzylpenicillin)
S
CH3
H
COOH
CH3
NH
H
O
H
CH2
O
Penicillin G
or
Benzyl penicillin
Penicillin is also known as Benzylpenicillin and it is also referred to
as gold standard penicillin, it is not acid resistant since it is acid
sensitive.
The three reasons for the acid
sensitivity of penicillin G.
 Ring strain
 Highly reactive carbonyl group
 Influence of the acyl side chain:
The acyl group open up the
lactam ring to causes self-
destruction due to its structural
composition.
Synthesis of Benzyl penicillin
CH2COCl
+
S
CH3
H
COOH
CH3
N
H2
H
O
H
phenylacetyl chloride
6 - APA
- HCl
S
CH3
H
COOH
CH3
NH
H
O
H
CH2
O
Penicillin G
or
Benzyl penicillin

USES:
It is an antibiotic used to treat a number of bacterial infections.
This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis, diphtheria, gas
gangrene, leptospirosis, cellulitis, and tetanus. It is not a first-line agent for pneumococcal
meningitis.
Benzylpenicillin is indicated for most wound infections, pyogenic infections of the skin, soft
tissue infections and infections of the nose, throat, nasal sinuses, respiratory tract and middle
ear, etc.

PENICILLIN-V (Phenoxy methyl penicillin)
S
N
CH3
CH3
COOH
NH
C
CH2
O
O
O
Penicillin V
The introduction of electron withdrawing group in
the side chain shows more acid stability than
penicillin G.
Hence it is more stable in acid of stomach, so it can
used orally.
Synthesis: S
N
CH3
CH3
COOH
N
H2
O
6 - APA
+ Cl
C
CH2
O
O
Phenoxy acetylchloride
-HCl
S
N
CH3
CH3
COOH
NH
C
CH2
O
O
O
Penicillin V
USES:
Penicillin V potassium is a slow-onset antibiotic that is used to treat many types of mild to
moderate infections caused by bacteria, including scarlet fever, pneumonia, skin infections,
and infections affecting the nose, mouth, or throat.
Penicillin V potassium is also used to prevent the symptoms of rheumatic fever.

AMPICILLIN
S
CH3
H
COOH
CH3
NH
H
O
H
O
N
H2
Ampicillin
Synthesis
Uses:
Ampicillin is used to treat certain infections that are caused by bacteria such as meningitis
(infection of the membranes that surround the brain and spinal cord).
Ampicillin is a penicillin antibiotic that is used to treat or prevent many different types of
infections such as bladder infections, pneumonia, gonorrhea, meningitis, or infections of the
stomach or intestines.
S
N
CH3
CH3
COOH
NH
C
HC
O
O
NH2
Ampicillin
CH COCl
NH2
+
amino(phenyl)acetyl chloride
S
N
CH3
CH3
COOH
N
H2
O
6 - APA
- HCl

AMOXICILLIN
Synthesis
S
CH3
H
COOH
CH3
NH
H
O
H
O
N
H2
O
H
Amoxicillin
CH COCl
NH2
O
H
+
S
CH3
H
COOSi(CH 3)3
CH3
N
H2
H
O
H
Trimethyl sylil ester of 6 - APA
S
CH3
H
COOH
CH3
NH
H
O
H
O
N
H2
O
H
Amoxicillin
amino(4-hydroxyphenyl)acetyl chloride
Uses:
Amoxicillin is an antibiotic. It's used to treat bacterial infections, such as chest infections
(including pneumonia), dental abscesses and urinary tract infections (UTIs).
It's used in children, often to treat ear infections and chest infections.

METHICILLIN
S
N
CH3
CH3
COOH
NH
C
CH2
O
O
OCH 3
OCH 3
Methicillin
It is a penicillinase resistant penicillin, the bulky methoxy groups
which are present on the phenyl ring of side chain act as steric shield
to protect from β-lactamase enzyme. At the same time steric shield
should not be too bulky. If it is too bulky it is also preventing the
penicillin from attacking the target enzyme transpeptidase.
It is not used much due to its adverse effect like intestinal nephritis
(kidney damage).
Uses:
Methicillin, also called meticillin, antibiotic formerly used in the treatment of bacterial
infections caused by organisms of the genus Staphylococcus.
Methicillin is no longer commercially available because of its side effects including interstitial
nephritis and kidney failure. Nowadays, methicillin is neither used for treatment nor for
susceptibility testing of gram-positive bacteria.

Structural Activity Relationship (SAR)
S
N
CH3
CH3
COOH
NH
C
O
O
R
H 1
2
3
4
5
6
7
1. The sulfur atom which is a present at position 1st is necessary for
activity, when it is oxidized to a sulfone or sulfoxide to improves
acid stability but decreases the activity.
2. The methyl groups present at position 2nd necessary for activity, if
any changes or substitution with other groups decreases the
activity.
3. The presence of carboxylic group at position 3rd is necessary for
activity, if it is changed to an alcohol or ester decreases the
activity.
4. The nitrogen present at position 4 must for antibacterial activity.

Structural Activity Relationship (SAR)
S
N
CH3
CH3
COOH
NH
C
O
O
R
H 1
2
3
4
5
6
7
5. No substitutions were allowed at 5th position otherwise produces
inactive compounds.
6. The different substitutions are allowed on the side chain of amide
at 6th position to show difference in activity.
The electron withdrawing group added to produce better acid
stability because it makes the amide oxygen less nucleophilic.
The addition of bulky groups on amide side chain produces more
stability towards β-lactamase enzymes.
7. The presence of carbonyl ring at 7th position must for antibacterial
activity.

CEPHALOSPORINS
Cephalosporins are the second major group of β-lactam, broad-spectrum,
penicillinase resistance antibiotics derived from the micro organism
Cephalosporium acremonium and chrysogenum’. These are closely related to the
penicillins in both structure and mode of action and are used to treat bacterial
infection.
WHY CEPHALOSPORINS?
 Broad spectrum of activity
 Stability to β-lactamase
 Oral and parenteral preparations
 Treat day to day as well as serious infections
 High safety profile

CEPHALOSPORINS LIMITATIONS
• Emerging resistance pattern
• Some III & IV generation cephalosporins were available only as parenteral
formulations
• Pharmacoeconomics

INTRODUCTION
In 1948, Abraham and his colleagues have isolated three principle antibiotic
components from cultures of fungus.
Cephalosporin P
Cephalosporin N
Cephalosporin C
1964 ,the first semi synthetic cephalosporin i.e. cefalothin was launched in the
Market by Eli Lilly and company.
Cephalosporins are second major group of β-lactam ,broad spectram,
penicillinase resistant antibiotics.
They were isolated from cultures of Cephalosporium acremonium by
italian scientist Giuseppe Brotzu in 1945.

BIOLOGICAL SOURCES
Cephalosporium acremonium is the most important source for the production of
cephalosporins.
Presently major source for the production of cephalosporins include…
 Cephalosporin C
 Penicillin V
 Cephamycin C
Cephalosporins are semi synthetically prepared from 7-amino cephalosporanic acid
(7-ACA).
S
N
O
O
CH3
O
NH
H H
O
O
NH2
O
H
O
H O
1
2
3
4
5
6
7
Cephalosporin C
S
N
O
O
CH3
O
N
H2
H H
O
H O
1
2
3
4
5
6
7
7-amino cephalosporanic acid

MECHANISM OF ACTION OF CEPHALOSPORINS
Identical to
penicillins…….
 Binding to
cephalosporin binding
proteins (PBP)
 Inhibition of
transpeptidation
process
 Activation of autolysin
enzyme

FIRST GENERATION CEPHALOSPORINS
 These drugs are very active against Gram +ve cocci (such as Pneumococci, Streptococci,
and Staphylococci).
 They do not cross BBB.
They offer advantageous over penicillins, they have greater stability to acid, β-lactamases,
good ratio of activity against Gram +ve and Gram –ve bacteria. However they are generally
poor in oral availability and are generally lower in activity.
The main disadvantage of cephalothin is the fact that the acetyloxy group at position 3rd is
readily hydrolysed by esterase enzyme to give less active alcohol.

CEPHALOTHIN
 It has less antibiotic activity than penicillin G against Gram + ve bacteria
 More activity than penicillin G against Gram – ve bacteria
 It can be used on patients who are allergic to penicillin
 Side chain acetoxy group is HOT POINT for metabolic inactivation.
USES:
Cephalothin tend to be broad-spectrum antibiotics that are effective against gram-
positive and many gram-negative bacteria, including Staphylococcus, Streptococcus,
and many strains of Escherichia coli. They have also been used to fight pulmonary
infections caused by Klebsiella pneumoniae
S
N
O
O
CH3
O
NH
H H
O
H O
O
S
Cephalothin

Cephaloridine
S
N
O
O
CH3
O
NH
H H
O
H O
O
S
Cephalothin
metabolism
S
N OH
O
NH
H H
O
H O
O
S
decrease activity
(Active)
S
N
O
NH
H H
O
H O
O
S
N
+
Cephaloridine
The acetoxy group present in cephalothin is important to the mechanism of inhibition and act
as good leaving group but after metabolism it produce alcohol group which act as much
poorer leaving group to reduce the activity.
Hence replacing the ester with a metabolically stable pyridinium group gives cephaloridine
which can act as a good leaving group for the inhibition mechanism but not cleaved by esters.

Cephradine
USES: Cefadroxil is used to treat certain infections caused by bacteria such
as infections of the skin, throat, tonsils, and urinary tract. Cefadroxil is in a class
of medications called cephalosporin antibiotics. It works by killing bacteria.
Cefadroxil
S
N
O
NH
H H
O
H O
O
NH2
Cephradine
S
N
O
NH
H H
O
H O
O
NH2
O
H
Cefadroxil
USES: This medication is a cephalosporin-
type antibiotic used to treat a wide variety of
bacterial infections (e.g., skin, ear, respiratory and urinary
tract infections). It works by stopping the growth of bacteria.
This antibiotic treats only bacterial infections.

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.

Cefoxitin
USES:
Cefoxitin injection is used to
treat infections caused by bacteria
including pneumonia and other lower
respiratory tract (lung) infections; and
urinary tract, abdominal (stomach area),
female reproductive organs, blood, bone,
joint, and skin infections.
S
N
O
O
NH2
O
NH
O
H O
O
S
OCH 3
Cefoxitin
Cephamycin
USES:
A semi-synthetic, broad-spectrum antibiotic
for parenteral administration used for the
treatment of serious bacterial infections,
such as urinary tract infection, blood
infection, bone and joint infection, and lower
respiratory tract infection.

Cefaclor
USES:
Cefaclor is used to treat
certain infections caused by bacteria,
such as pneumonia and other lower
respiratory tract (lung) infections;
and infections of the skin, ears,
throat, tonsils, and urinary tract.
Cefuroxime
USES:
It is an antibiotic used to treat and prevent a
number of bacterial infections. These include
pneumonia, meningitis, otitis media, sepsis,
urinary tract infections, and Lyme disease.

S
N S
O
NH
O
H O
O
N
N
N
N
OH
Cefamandole
S
N S
O
NH
O
H O
O
N
N
N
N
CH2COOH
CH2NH2
Ceforanide
S
N S
O
NH
O
H O
O
OCH 3
S
S
O
H
O
N
H2
O
N
N
N
N
Cefotetan
S
N S
O
NH
O
H O
O
OCH 3
N
N
N
N
S
NC
Cefmetazole

THIRD GENERATIONCEPHALOSPORINS
Expanded Gram-negative coverage
Able to cross the BBB.
Anti-pseudomonal activity.
S
N
CH
CH2
O
NH
O
H O
O
N
S
N
H2
NOCH2COOH
Cefixime
S
N
O
O
O
NH
O
H O
O
N
S
N
H2
NOCH3
Cefotoxime
S
N S
O
NH
O
H O
O
N
S
N
H2
NOCH3
N
N
N
OH
O
Ceftriaxone

Cefotaxime
USES:
Cefotaxime is an antibiotic used to treat a
number of bacterial infections. Specifically it is
used to treat joint infections, pelvic
inflammatory disease, meningitis, pneumonia,
urinary tract infections, sepsis, gonorrhea, and
cellulitis. It is given either by injection into a
vein or muscle.
Ceftriaxone
USES:
Ceftriaxone injection is used to treat
certain infections caused by bacteria such as
gonorrhea (a sexually transmitted disease), pelvic
inflammatory disease (infection of the female
reproductive organs that may cause
infertility), meningitis (infection of the membranes
that surround the brain and spinal cord)
S
N
O
O
O
NH
O
H O
O
N
S
N
H2
NOCH 3
Cefotoxime
S
N S
O
NH
O
H O
O
N
S
N
H2
NOCH 3
N
N
N
OH
O
Ceftriaxone

Cefixime
USES:
Cefixime is used to treat
certain infections caused by bacteria such
as bronchitis (infection of the airway tubes
leading to the lungs); gonorrhea (a sexually
transmitted disease); and infections of the
ears, throat, tonsils, and urinary tract.
Cefdinir
USES:
Cefdinir is used to treat
certain infections caused by bacteria such
as bronchitis (infection of the airway tubes
leading to the lungs); pneumonia;
and infections of the skin, ears, sinuses,
throat, and tonsils.
S
N
CH
CH2
O
NH
O
H O
O
N
S
N
H2
NOCH2COOH
Cefixime
S
N
CH
CH2
O
NH
O
H O
O
N
S
N
H2
N
O
H
Cefdinir

S
N
O
NH
O
H O
O
N
S
N
H2
NOCH 3
Ceftizoxime
S
N
O
NH
O
H O
O
N
S
N
H2
COOH
Ceftibuten

FOURTH GENERATION CEPHALOSPORINS
 Zwitterionic compounds.
 Good affinity for the transpeptidase enzyme.
 Low affinity for some β-lactamases.
 Cross BBB and effective in meningitis.
S
N N
+
O
NH
O
H O
O
N
S
N
H2
NOCH 3
Cefipirome
S
N N
+
O
NH
O
H O
O
N
S
N
H2
NOCH 3
Cefipime

Cefepime
USES:
Cefepime injection is used to treat certain
infections caused by bacteria
including pneumonia, and skin, urinary
tract, and kidney infections.
Cefepime injection is used in combination
with metronidazole (Flagyl) to treat
abdominal (stomach area) infections.
Cefpirome
USES:
It can be given for
septicaemia, infections of the lower
respiratory tract, skin and soft tissues and
complicated infections of the urinary tract.
Cefpirome can also be used to
treat infections in neutropenic patients.
S
N N
+
O
NH
O
H O
O
N
S
N
H2
NOCH3
Cefepime
S
N N
+
O
NH
O
H O
O
N
S
N
H2
NOCH3
Cefpirome

FIFTH GENERATION CEPHALOSPORINS
Active against
• methicillin-resistant -Staphylococcus aureus
• penicillin-resistant - Streptococcus pneumoniae
S
N
O
NH
O
H O
O
N
N
S
N
H2
NOH N
O
N
H
Ceftobiprole
USES:
Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of
hospital-acquired pneumonia (excluding ventilator-associated pneumonia) and community-
acquired pneumonia.

STRUCTURE -ACTIVITY RELATIONSHIP:
37
Basic chemistry:β-lactam ring+Dihydrothiazine ring
Variable group
Variable group
7-Aminocephalosporanic acid

USES
Adverse effects:
Disulfiram- like effect
Nephrotoxicity
Bleeding
Allergic reactions
Phlebitis
IMPETIGO CELLULITIS P.aeruginosaINFECTIONS
PNEUMONIA BACTERIALMENINGITIS

CEPHALOSPORINS ADVANTAGES OVER PENICILLINS:
 Increased acid stability compare to penicillins.
 Most of the drugs have better absorption than penicillins.
 Broad antimicrobial spectrum.
 Increased activity against resistant microorganisms.
 Decreased allergenicity.
 Increased tolerence than penicillins.

 Cephalosporins are more resistant to β-lactamase than penicillins.
 Cephalosporins are high potent with broad spectrum of activity.
 Cephalosporins are equally effective against both Gram +ve and Gram -ve organisms but
penicillins are mostly active against Gram +ve organisms.
 Cephalosporins are preferred against acute pneumonia over penicillins
 Oral and parenteral preparations more acceptable than penicillins.

 They have high safety profile
 Cephalosporins treat day to day and as well as some serious infections.
 Increased acid stability compares to penicillins.
 Most of the drugs have better absorption than penicillins.
 Increased activity against resistant microorganisms.
 Decreased allergenicity.
 Increased tolerance than penicillins.

β-LACTAMASE INHIBITORS
 Has negligible antibacterial activity.
 Given with Penicillins which increases spectrum of activity.
 Microbial resistance to beta lactamase enzyme.
S
N
O
Beta-lactamase
S
N
H
O OH

• Clavulanic acid:
 Isolated from Streptomyces clavuligerus.
1st naturally occurring β-lactam ring that
was not fused to a ‘S’ containing ring.
• Sulbactum:
 β-lactamase disabiling agent.
 Prepared by partial chemical
synthesis from penicillins.

Tazobactum:
Co-administered with Piperacillin.
Has little or no antibacterial activity.

Combinations of penicillins with β lactamase inhibitors:
Amoxicillin + Clavulanic acid = Clavulin
Ticarcillin + Clavulanic acid = Timentin
Piperacillin + Tazobactam = Tazocin
Ampicillin + Sulbactum = Unasyn

 Streptococcal infections
 Pneumococcal infections
 Meningococcal infections
 Gonorrhoea
 Syphilis
 Diphtheria
 Tetanus
TOXICITY:
 Nausea ,Dizziness ,Head ache ,skin rashes ,Bronchospasm ,
vasculitis , inflammation of blood vessles.
Hypersensitivity or allergic reactions.
USES:

 Carbapenems are a class of highly effective antibiotic agents commonly used for the
treatment of severe or high-risk bacterial infections. This class of antibiotics is usually
reserved for known or suspected multidrug-resistant (MDR) bacterial infections.
 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
INTRODUCTION

IMIPENEM
IMIPENEM has a wide spectrum with good activity many
gram negative rods including P.aeruginosa, gram positive
organisms and anaerobes.
Imipenem is inactivated bydehydropeptidases in renal
tubules, result in low urinary concentrations.
(Imipenem)
USES:
Imipenem and cilastatin injection is used to treat certain serious infections that are
caused by bacteria, including endocarditis (infection of the heart lining and valves) and
respiratory tract (including pneumonia), urinary tract, abdominal (stomach area),
gynecological, blood, skin, bone, and joint infections.

Meropenem
USES:
Meropenem injection is used to treat skin and abdominal (stomach
area) infections caused by bacteria and meningitis (infection of the membranes that
surround the brain and spinal cord) in adults and children 3 months of age and older.
Meropenem injection is in a class of medications called antibiotics.

Ertapenem
USES:
Ertapenem injection is used to treat certain serious infections, including pneumonia and
urinary tract, skin, diabetic foot, gynecological, pelvic, and abdominal (stomach
area) infections, that are caused by bacteria. It is also used for the prevention
of infections following colorectal surgery.

Carbapenemswhich tend to be more common with imipenem are nausea, vomiting, diarrhea,
skin rashes, and reactions at the infusion sites
Excessive levels of imipenem in patients with renal failure may lead to seizures
Patients allergic to penicillins may be allergic to carbapenems.
ADVERSE EFFECTS

INTRODUCTION
 Monobactams are drugs with a monocyclic β-lactam ring.
 They are relatively resistant to beta-lactamases and active against Gram-negative rods
(including Pseudomonas and Serratia).
 They have no activity against Gram-positive bacteria or anaerobes.
Examples
Aztreonam , Tigemonam.

AZTREONAM
 Aztreonam is given i.v.
 The half-life is 1–2 hours and is greatly prolonged in renal failure.
 Penicillin-allergic patients tolerate aztreonam without reaction
(Aztreonam)
USES:
Aztreonam injection is used to treat certain infections
that are caused by bacteria, including respiratory tract
(including pneumonia and bronchitis), urinary tract,
blood, skin, gynecological, and abdominal (stomach
area) infections, that are caused by bacteria.

Tigemonam
USES:
It is a newer monobactam which is active orally and highly resistant to β-lactamase enzyme
It is a valuable agent for the oral treatment of U.T.I and other non-life threatening infections caused
by β-lactamase producing gram –ve bacteria like (e.g. Neisseria, pseudomonas) bacteria.
Siderophore-conjugated monobactams show promise for the treatment of multi drug-resistant
pathogens.

TETRACYCLINES
These are potent broad spectrum antibiotics (effective against wide variety of M.O) derived
from the culture of STREPTOMYCES bacteria and are effective against wide variety
infections.
These are mainly designed for ORAL route but parenteral and topical forms are also available.
STRUCTURE OF TETRACYCLINES
The Tetracyclines are amphoteric compounds forming salts with either acids or bases. It exists
mainly as zwitter ions in neutral solutions
O
H
OH
H3C H H
N(CH3)2
OH
NH2
O
OH
OH
O O

STRUCTURE OF TETRACYCLINES
S. No Name R1 R2 R3 R4
1 Tetracyclines H OH CH3 H
2 Chlortetracycline Cl OH CH3 H
3 Oxytetracycline H OH CH3 OH
4 Demeclocycline Cl OH H H
5 Methacycline H CH2 - OH
6 Doxycycline H CH3 H OH
7 Minocycline N(CH3)2 H H H
8 Meclocycline Cl CH2 - OH
OH
R
3
R
2 N(CH 3)2
OH
NH2
O
OH
OH
O O
R
1 R
4
H
H
1
2
3
4
5
6
7
8
9
10 11 12

SAR OF TETRACYCLINES
1. C-1 substituents: the keto-enol system of the A-ring is necessary for antibacterial activity.
2. C-2 substituents: the carboxamide moiety is present in all naturally occurring tetracyclines
and this group is crucial for antibacterial activity. The unsubstituted amide is best or mono-
substitution also acceptable for activity.
3. C-3 substituents: in conjugation with the C-1 position, the keto-enol conjugated system is
important for antibacterial activity.
4. C-4 substituents: the naturally occurring tetracyclines contain α-C-4 dimethylamino
substituent that favourably contributes to the keto-enolic character of the A ring.
Replacement of dimethylamino group with a hydrazone, oxime, or hydroxyl group leads to
loss of activity, probably due to the increase in heteroatom basicity.
OH
OH
NH2
O
OH
OH
O O
H
H
 
1
2
3
4
5
6
7
8
9
10 11 12
A
B
C
D
4a
5a
6a
10a 11a
12a

5. C-4a substituents: the α-hydrogen at C-4a position of tetracyclines is necessary for useful
antibacterial activity.
6. C-5 substituents: many naturally occurring antibacterial tetracyclines have unsubstituted
methylene moiety at the C-5 position. However, oxytetracycline contain C-5- α-hydroxyl
group and was found to be a potent compound, and has been modified chemically to
some semi-synthetic tetracyclines. Alkylation of the C-5 hydroxyl group results in a loss
of activity.
7. C-5a substituents: the configuration of the naturally occurring tetracyclines places the C-
5a hydrogen atom in an α-configuration. Epimerization is detrimental to antibacterial
activity.
OH
OH
NH2
O
OH
OH
O O
H
H
 
1
2
3
4
5
6
7
8
9
10 11 12
A
B
C
D
4a
5a
6a
10a 11a
12a

8. C-6 substituents: The C-6 is tolerant of a variety of substituents. The majority of
tetracyclines have an α-methyl group and a β-hydroxyl group at this position.
Demeclocycline is a naturally occurring C-6 demethylated chlortetracycline with
excellent activity. This C-6 methyl group contributes little to the activity of tetracycline.
Similarly, the C-6 hydroxyl group also appear to offer little in terms of antibacterial
activity, removal of this group affords doxycycline, which is a excellent antibacterial.
9. C-7 and C-9 substituents: the nature of the aromatic D-ring predisposes the C-7 position
to electrophilic substitution, and nitro or halogen groups have been introduced.
10. The C-7 acetoxy, azido, and hydroxyl tetracyclines are lower the antibacterial activity.
11. C-10 substituents: The C-10 phenolic moiety is absolutely necessary for antibacterial
activity.
OH
OH
NH2
O
OH
OH
O O
H
H
 
1
2
3
4
5
6
7
8
9
10 11 12
A
B
C
D
4a
5a
6a
10a 11a
12a

12. C-11 substituents: The C-11 carbonyl moiety is part of one of the conjugated keto-enol
system required for antibacterial activity.
13. C-12a substituents: The presence of hydroxyl group is needed for antibacterial activity.
OH
OH
NH2
O
OH
OH
O O
H
H
 
1
2
3
4
5
6
7
8
9
10 11 12
A
B
C
D
4a
5a
6a
10a 11a
12a

GENERAL MECHANISM OF ACTION OF TETRACYCLINES
The tetracyclines are primarily bacteriostatic and
inhibit protein synthesis by binding to 30 S
ribosomes in susceptible organism.
Subsequent to such binding of aminoacyl-t-RNA
to the m-RNA ribosome complex this leads to the
inhibition of transfer of genetic information from
t-RNA to m-RNA. Hence no translation(m-RNA
to protein) or protein synthesis occurs in the m-
RNA ribosomal complex.
It also binds to some extent to the 50S
ribosomal subunit. This binding is reversible
in nature.

TETRACYCLINE
It is obtained from fermentation of STREPTOMYCES AUREFACIENS or it is also obtained
from catalytic selective HYDROGENOLYSIS of 7-chloro atom of Chlortetracycline
O
H
OH
H3C H H
N(CH3)2
OH
NH2
O
OH
OH
O O
ADR:
Oesophageal ulceration, dry and flaky skin when applied externally, Nausea, vomiting and
diarrhoea.
USES:
Tetracycline is used to treat infections caused by bacteria including pneumonia and
other respiratory tract infections; certain infections of skin, eye, lymphatic, intestinal, genital
and urinary systems; and certain other infections that are spread by ticks, lice, mites, and infected
animals.
O
H
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
Cl
Hydrogenolysis at
C7 position
O
H
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
Chlortetracycline Tetracycline

CHLORTETRACYCLINE
It is obtained from “Streptomyces Aureofaciens” present in soil sample collected from
sanborn field at the university of missouri
ADR:
Polyurea, Photoallergic reactions, Nausea, Vomiting and Diarrhoea etc.
USES:
In veterinary medicine, chlortetracycline is commonly used to treat conjunctivitis in cats, dogs
and horses. It is also used to treat infected wounds in cattle, sheep an pigs, and respiratory tract
infections in calves, pigs and chickens.
OH
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
Cl
Chlortetracycline
OH
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
Cl
Chlortetracycline
OH
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
Tetracycline
Selective halogenation
at C7 position

OXYTETRACYCLINE
It is isolated from “streptomyces rimosus”
ADR:
Gastrointestinal disturbance, Photoallergic reactions, Anorexia, Nausea, Vomiting and Diarrhoea
etc.
USES:
Oxytetracycline is an antibacterial medicine. This means that it stops infections caused by
germs (bacteria). It is prescribed as a treatment for chest infections such as pneumonia, and
also for some mouth infections.
O
H
OH
H3C N(CH3)2
OH
NH2
O
OH
OH
O O
OH
Oxytetracycline

DOXCYCLINE
It is produced by catalytic hydrogenation
(reduction) of methacycline.
ADR:
Gastrointestinal upset, permanent staining of teeth, rash, Nausea, Vomiting and Diarrhoea etc.
USES:
Doxycycline is an antibiotic. It's used to treat infections such as chest infections, skin
infections, rosacea, dental infections and sexually transmitted infections (STIs), as well as a
lot of other rare infections. It can also be used to prevent malaria if you're travelling abroad.
O
H
CH3 N(CH3)2
OH
NH2
O
OH
OH
O O
OH
Doxycycline
O
H
CH3 N(CH3)2
OH
NH2
O
OH
OH
O O
OH
Doxycycline
OH
CH2 N(CH3)2
OH
NH2
O
OH
OH
O O
OH
Methacycline
H2 / Ni
reduction

MINOCYCLINE
It is most potent tetracycline currently used in therapy
ADR:
Oesophageal ulceration, dizziness, loss of hearing, Nausea, Vomiting etc.
USES:
Minocycline is used to treat infections caused by bacteria including pneumonia and
other respiratory tract infections; certain infections of the skin, eye, lymphatic, intestinal,
genital, and urinary systems; and certain other infections that are spread by ticks, lice, mites,
and infected animals.
OH
N
OH
NH2
O
OH
OH
O O
N
CH3
H3C CH3
H3C
Minocycline

MACROLIDE ANTIBIOTICS
O O
O
H OH
O
O
O
H
O
Neutral sugar
Amino sugar
1
2
3
4
5
6
7
8
9
10
11
12
13
14
14 - membered macrolide ring
Presence of a Macrocyclic (14, 15 or 16 membered) Lactone ring (Macrolide ring). It is a non-
polar and stainless stable ring.

MACROLIDE ANTIBIOTICS
These are defined as a group of Antibiotics containing a MACROLYTIC LACTONE ring to
which a neutral sugar and amino sugar are attached.
STRUCTURE
The main structural features of this class are
 Presence of a Macrocyclic (14, 15 or 16 membered) Lactone ring (Macrolide ring). It is a
non-polar and stainless stable ring.
 Presence of a Ketone and Hydroxyl functional group.
 Presence of basic Neutral sugars and Amino sugars (6-deoxy sugar) attached by means of
glycosidic linkages to the Lactone ring.

MOA:
Macrolide binds to 50s subunit of the bacterial ribosome to prevent the TRANSLATION of
PEPTYDYL t- RNA from A site to P site. The growth of peptide chain blocked and prevent the
protein synthesis.

ERYTHROMYCIN
O O
O
H OH
O
O
O
H
O
O
O
H
N
O
OH
OH
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Erythromycin
USES:
1. Used in the treatment of Upper and Lower RTI caused by Gram +ve bacteria.
2. Used in the treatment of Tetanus caused by Clostridium Tetani. Especially in those patients
who are allergic to penicillin.
3. Used in the treatment of SYPHILIS in pregnant women’s who are allergic to Penicillin.
4. Also used in chemotherapy of SABE (Sub Acute Bacterial Endocarditis)
5. It is also used in the treatment of GONORRHOEA.
It is isolated from culture of STREPTOMYCES ERYTHREUS
ADR:
Rash, Utricaria, Nausea, Vomiting and GIT discomfort.

AZYTHROMYCIN
O O
O
H
O O
O
O
H
N
O
OH
OH
N
OH
OH
Azythromycin
It is a semisynthetic derivative of Erythromycin.
It is a nitrogen containing 15- membered macrolide
ring and which is also known as Azalides. It is more
stable than other macrolide antibiotics.
ADR:
Nausea, Vomiting, Abdominal pain and Flatulence.
USES:
1. Useful in the treatment of Respiratory Tract Infections caused by H. Influenza.
2. Useful in the treatment of Gram +ve bacterial infections such as URETRITIS.
3. It also used in Sexually Transmitted Diseases such as SYPHILIS & GONORRHOEA.

CLARYTHROMYCIN
O O
O
H OCH3
O
O
O
H
O
O
O
H
N
O
OH
OH
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Clarythromycin
Chemically it is 6-methyl ether of Erythromycin. It is prepared
by simply methylating Erythromycin at 6-OH group.
This semisynthetic derivative fully retains the antibacterial
activity of Erythromycin with increase acid stability and oral
bioavailability and reduce GIT side effects.
SYNTHESIS:
O O
O
H OCH3
O
O
O
H
O
O
O
H
N
O
OH
OH
Clarythromycin
CH3I
O O
O
H OH
O
O
O
H
O
O
O
H
N
O
OH
OH
Erythromycin

USES:
1. Clarithromycin is effective against infections caused by Haemophilus Chlamydia and
Legionella.
2. It shows its potent activity against intracellular complexes such as those of Mycobacterium
Avium intracellular complex.
3. It has greater Antibacterial activity than Erythromycin.
ADR:
GIT upset, Altered taste, Headache and Hallucination.

LINCOMYCINS
Lincomycin’s are Sulfur – containing antibiotics isolated from STREPTOMYCES
LINCOLENSIS. These are most active and medicinally useful compounds.
MOA:
Lincomycin’s binds to the 50s ribosomal subunit to inhibit protein synthesis. They may be
bacteriostatic or bactericidal depending on various factors such as concentration of antibiotics
etc.

LINCOMYCIN
O
CH3
H
NH
H
O
H
OH
H
H
OH
OH
H
SCH 3
C
O
N
CH3
H
C3H7
Lincomycin
USES:
1. It is used to treat wide variety of Upper Respiratory, Skin and tissue infections.
ADR:
Hypotension, Vertigo, Dermatitis, Rash and utricaria.

CLINDAMYCIN
O
CH3
H
NH
H
Cl
OH
H
H
OH
OH
H
SCH 3
C
O
N
CH3
H
C3H7
1
2
3
4
5
6
7
Clindamycin
Replacement of 7 – OH group of Lincomycin with Chlorine
gives CLINDAMYCIN with enhanced antibacterial activity.
ADR:
Diarrhoea, Abdominal pain, Nausea and vomiting.
USES:
1. It is used in the treatment of wide variety of upper RTI, skin and tissue infections.
2. It is also active against various infections caused by Streptococci, Staphylococci and
Pneumococci.

CHLORAMPHENICOL
MOA:
It inhibit bacterial protein synthesis by interfering with transfer of the elongating peptide chain
to the newly attached aminoacyl-tRNA at the ribosomal mRNA complex.
It is specifically attaches to the 50S ribosome and thus may hinder the access of aminoacyl-
tRNA to the acceptor site for amino acid incorporation.
It also prevent peptide bond formation.
Oesophageal ulceration, dizziness, loss of hearing, Nausea, Vomiting etc.
ADR:
Aplastic anemia, Bone marrow suppression, Leukemia, Gray baby syndrome, Hypersensitivity
reactions, Neurotoxic reactions etc.
USES:
Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections.
This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a
vein, it is used to treat meningitis, plague, cholera, and typhoid fever.
O2N CH CH NH C CHCl 2
CH2OH
OH
O
2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]acetamide

AMINOGLYCOSIDE ANTIBIOTICS
Most of the Aminoglycosides antibiotics obtained from genus “STREPTOMYCES”.
Most important Aminoglycoside antibiotic is Streptomycin, several other closely related
structures are Kanamycin, Neomycin, Gentamycin etc.
Spectrum of Antimicrobial Activity
 Aminoglycosides are broad-spectrum antibiotics effective in:
1. Systemic Infections caused by aerobic G(-) bacillus (klebsiella, proteus, enterobacters).
2. Tuberculosis, Brucellusis, Tularaemia and yersinia infections.
3. Amoebic dysentery, shigellosis and salmonellosis.
4. Pneumonia and urinary infections caused by Pseudomona aeroginosa.
5. G(+) and G(-) aerobic cocci except staphylococci and anaerobic bacteria are less
susceptible.

Introduction
Antibiotics contain an aminocyclitol moiety to which amino sugars are glycosidically
linked.
They may be more correctly called aminocyclitol antibiotics.
O
O
O
O
H2C
NH2
H2N
OH
NH2
HO
NH2
HO
NH2
Tobramycin
HOH2C
HO
1
1''
2''
3''
4''
5''
1'
5'
4'
3' 2'
3
4
5 6
6'
2
6''
O
O
O
O
R1H2C
HO
HO
R2
H2N
OH
NH2
HOH2C
HO
NH2
HO
1''
2''
3''
4''
5''
6''
1'
2'
3'
4'
6'
5'
1
2
3
4
5 6
Kanamycins

Aminocyclitols???
Cyclohexanes with several substituted or unsubstituted amino and hydroxyl groups which
bring them high water solubility.
Streptidine and Streptamine can be called 1,3-diguanidino and 1,3-diamino inositol,
respectively.
NH2
OH
HO
H2N
NH2
OH
HO
H2N
OH
H2N
HO
HO
HO
HO
OH
NHCH3
H3CO
1
2
3
4
5
6
1
2 3
4
5
6
1
2
3
4
5
6
H
N
OH
HO
HN
HO
OH
1
2
3
4
5
6
NH
NH2
NH
H2N
Streptamine
Streptidine
2-Deoxystreptamine
NHCH3
OH
HO
1 2
3
4
5
6
OH
Spectinamine Fortamine

All have an aminohexose as the amino sugar and some have a pentose as an extra sugar.
O
O
O
O
O
O
OH
CH2OH
H2N
NH2
HO
NH2
HO
HO
OH
HO
HO
R1
R2 NH2
Paromomycin I: R1= H; R2= CH2NH2
Paromomycin II: R1= CH2NH2; R2= H
1
2
3
3
4
5 6
1'
2'
3'
4'
5'
6'
1
2
3
4
4 5
1
2

Mechanism of Action of Aminoglycosides
They act by inhibiting the synthesis of proteins in microorganisms to carryout their
BACTERICIDAL action . Generally they act in either of the following ways.
They may block the initiation of the synthesis of proteins at the initial stage itself by
blocking the 30S-50S complex at the starting or initiation codon i.e. AUG of m-RNA and
prevent further TRANSLATION process to prevent protein synthesis.
They may directly bind to the 30S subunit of the ribosome and cause misreading of the m-
RNA codons, which results in premature termination of the translation process, where the
ribosomal complex detaches from the m-RNA resulting in formation of an incomplete
protein.
They may also act by incorporating incorrect or unwanted amino acids in the peptide chain
leading to the formation of unwanted or abnormal or non functional protein.
The all above mechanism would lead to the death of Micro –organisms.

Therapeutic Agents
O
O
O
O
R1H2C
HO
HO
R2
H2N
OH
NH2
HOH2C
HO
NH2
HO
1''
2''
3''
4''
5''
6''
1'
2'
3'
4'
6'
5'
1
2
3
4
5 6
Kanosamine
2-Deoxystreptamine
Kanamycin A: R1= NH2 ; R2 = OH
Kanamycin B: R1 = NH2 ; R2 = NH2
Kanamycin C: R1= OH; R2 = NH2
III
II
I
Isolated from cultures of Streptomyces kanamyceticus. The least toxic member in the market
is kanamycin A.
It is used for the treatment of GI infections, such as dysentery and systemic G(-) bacillus
infections caused by klebsiella, proteus, enterobacters.
For disinfection of GI before an operation.
Kanamycin

Amikacin
O
O
O
O
H2NH2C
HO
HO
OH
H2N
OH
NH2
HOH2C
HO
NH
HO
1''
2''
3''
4''
5''
6''
1'
2'
3'
4'
6'
5'
1
2
3
4
5 6
Amikacin
C C
O
CH2 CH2 NH2
OH
H
2
2-Deoxystreptamine
Kanosamine
A semisynthetic derivative of kanamycin A.
It is used in the treatment of infections caused by Mycobacterium tuberculosis, Yersinia
tularensis, Pseudomona aeroginosa.
The suffix “micin” denotes its origin.

Tobramycin
• Isolated from cultures of Streptomyces tenebrarius.
• Antimicrobial activity against resistance P.aeroginosa.
• Used to treat eye infections.
O
O
O
O
H2C
NH2
H2N
OH
NH2
HO
NH2
HO
2-Deoxystreptamine
Tobramycin
HOH2C
HO
1
1''
2''
3''
4''
5''
1'
5'
4'
3' 2'
3
4
5 6
2
6''
Lacks 3`-OH
APH Resistant

Gentamicin
Isolated from cultures of Micromonospora purpurea.
The suffix “micin” denotes its origin.
It is used against urinary infections caused by G(-) and pseudomona.
Also used for various skin infections and also external eye infections.
O
O
O
O
HC
NH2
H2N
OH
NH
H3C
NH2
HO
1''
2''
3''
4''
5''
1'
2'
3'
4'
6'
5'
1
2
3
4
5 6
Garosamine
2-Deoxystreptamine
Gentamicin C1: R1=R2 = CH3
Gentamicin C2: R1 = CH3 ; R2 = H
Gentamicin C1a: R1=R2 = H
OH
CH3
NHR2
R1
Lacks 3`-OH
APH Resistant
Axial and tertiary 4``-OH instead of
equatorial secondary 4``-OH in Kanamycin
ANT Resistant
Secondary amino group at 6`-NH2 in
Gentamycin C1, spacial hynderance
AAC Resisistant
I
II
III

Neomycin
O
O
O
O
O
O
OH
CH2OH
H2N
NH2
HO
NH2
HO
HO
NH2
HO
HO
H2NH2C
R2 NH2
2-Deoxystreptamine
Neosamine C
Neosamine C
1
2
3
3
4
5
6
1'
2'
3'
4'
5'
6'
1
2
3
4
4 5 1
2
D-Ribose
Neomycin
Isolated from cultures of Streptomyces fradia along with an antifungal subsance: Fradicin.
Effective against GI and dermal infections.

Streptomycin
O
O
H
N
HO
OH
OH
NH
NH
H2N
O
HO
H3C
CHO
O NHCH3
OH
HO
HO
H2N
HN
Streptidine
L-Streptose
N- Methyl-L-Glucosamine
Streptomycin
1''
2'
3'
4'
1
2
3 4
1'
2''
3''
4''
5''
6
5
Has a different aminocyclito (a 1,3-diguanidinoinositol).

Streptomycin continued
Isolated from cultures of Streptomyces griseus.
It was introduced against tuberculosis in 1943, kanamycin and amikacin are effective against
tuberculosis, but not as much as streptomycin.
Streptomycin brought Waxman the Noble prize in 1952.

Spectinomycin
An unusual aminoglycoside isolated from cultures of streptomyces spectabilis.
The sugar portion has a carbonyl group and is fused through glycosidic bonds to the
aminocyclitol portion, spectinamine.
It is used in a single dose against Neisseria gonhorea.
O
O
O
CH3
O
H3CHN
OH
NHCH3 OH
HO
Spectinomycin
Sugar
Spectinamine

SAR OF AMINO SUGAR RING
O
NH2
O
H
HO
NH2
1
2
3
4 5
6
 It is the most important component of Aminoglycoside ring system and
is essentially required for the Broad-Spectrum Antibacterial activity of
the aminoglycoside antibiotics.
 Presence of amino group at 2nd and 6th position of the ring is required
for the antibacterial activity. The diamino substitution is most essential
for activity.
Eg. Kanamycin-B having the amino substitution at 6th and 2nd position
is more active than Kanamycin – A (which is having OH- substitution
at 2nd and amino substitution at 6th position)

SAR OF AMINO SUGAR RING
O
NH2
O
H
HO
NH2
1
2
3
4 5
6
 Presence or absence of -OH group at 3rd or 4th position or at both doesn’t effect the
antibacterial activity.
 Substitution of Methyl group at 6th position leads to an increase in enzyme resistance but
doesn’t change the activity.
 The 6th and the 2nd position of the ring system form the major sites of target for the action of
the bacterial inactivating enzyme system.
 The presence of Amino group is more common at 6th position rather
than at 2nd position.
Eg. Kanamycin – A having 6-NH2, 2-OH substitution is more
active than Kanamycin – C (6- OH, 2- NH2).

 William O. Foye.,Textbook of Medicinal Chemistry,Pg no: 1089 -1106
 Sriram., Medicinal Chemistry, Pg no: 295-309.
 Kadam., Textbook of Medicinal Chemistry, Pg no: 68-82.
 Ilango., Principles of Medicinal chemistry(vol.1), Pg no: 121-143.
 G.L.Patrick., Introduction to Medicinal Chemistry, Pg no:388-415.
 Good man And Gil Man’s ;The Pharmacology Basis Of Therapeutics Tenth Edition
page no 1189-1225.
 JH Block & JM Beale., Wilson & Giswold’s Textbook of Organic Medicinal
Chemistry & pharmaceutical chemistry 11th Edition, 2004.
Reference:

Antibiotics.pptx

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