This document provides an overview of antibiotics. It begins by defining antibiotics as substances produced by microorganisms or synthesized that selectively kill or inhibit the growth of other microorganisms. Antibiotics can be classified in several ways, including by their mechanism of action, spectrum of activity, chemical structure, and types of organisms treated. Common mechanisms of action include inhibition of cell wall synthesis, protein synthesis, and nucleic acid synthesis. The document then discusses the history of antibiotic discovery, including early pioneers like Fleming who discovered penicillin, and Waksman who discovered streptomycin through systematic soil screening. It covers the development of important classes of antibiotics like penicillins, cephalosporins, and aminoglycosides. In summary
2. What is an antibiotic?
“Antibiotic” is from antibiosis, meaning against life.
•Substances produced by microorganisms,
•Selectively suppress the growth , kill other
microorganisms at very low concentrations.
“Substances derived from a microorganism or produced
synthetically (Sulfonamides & Quinolones) to kill or
suppress the growth of other microorganisms"
Prof.Suryawanshi C.P.
3. Antibiotics are classified by several ways:
• On the basis of mechanism of action
• On the basis of spectrum of activity
• On the basis of mode of action
• On the basis of chemical Structure
• On the basis of types of organism treated
Prof.Suryawanshi C.P.
4. 1. Inhibition of cell wall synthesis:
• Penicillins, Cephalosporins, Bacitracin & Vancomycin
2. Inhibition of functions of cellular membrane:
• Polymyxins
3. Inhibition of protein synthesis:
• Chloramphenicol, Macrolides & Clindamycin
• Tetracyclines & Aminoglycosides
4. Inhibition of nucleic acid synthesis:
• Quinolones
• Rifampin
5. Inhibition of folic acid synthesis:
• Sulfonamides & trimethoprim
Prof.Suryawanshi C.P.
6. Antimicrobial spectrum: the scope that a drug kills or
suppresses the growth of microorganisms.
Narrow-spectrum: The drugs that only act on one kind
or one strain of bacteria.(Isoniazide)
Broad-spectrum: The drugs that have a wide
antimicrobial scope.(Tetracycline &
Chloramphenicol)
Prof.Suryawanshi C.P.
13. Antonie van Leeuwenhoek
(Delft,1632-1723)
Firstto observeand
describe singlecelled
organisms which he first
referredto as animalicula,
and which we now know to
be microorganisms
(protozoa, bacteria).
Bacteria in tooth plaque (1683)
Prelude to Antibiotics:
Leeuwenhoek & The Birth of Microbiology
Prof.Suryawanshi C.P.
14. Prelude to Antibiotics:
(Pasteur, Koch & The Germ Theory of Disease)
Louis Pasteur
(Strasbourg, 1822-1895)
Showedthatsome
microorganisms
contaminatedfermenting
beveragesand concluded
that microorganisms
infected animals and
humansas well.
RobertKoch
(Berlin,1843-1910)
Discovered Bacillus
anthracis,Mycobacterium
tuberculosis,Vibrio
cholerae and developed
“Koch’s Postulates".
NobelPrice in Medicine
1905 for work on
tuberculosis.
Koch’sPostulates: (1890)
To establishthata
microorganism is the
cause of a disease,it
mustbe:
1) found in all casesof
the disease.
2) isolated from the host
and maintained in pure
culture.
3) capableof producing
the originalinfection,
even after several
generations in culture.
4) recoverablefrom an
experimentallyinfected
host.
Prof.Suryawanshi C.P.
15. Invention of Modern Drug Discovery: Ehrlich & The Magic Bullet
Paul Ehrlich (Frankfurt, 1854-1915)
Synthesized and screened hundredsof
compounds to eventually discover and
develop the firstmodern chemotherapeutic
agent (Salvarsan,1909)for the treatmentof
syphillis (Treponema pallidum).
NobelPrice in Medicine 1908 forwork
on immunity (with Mechnikov).
MagicBullet:Compoundthat selectivelytargets a disease causing
organism while having no negative effecton human tissue.
Salvarsan in solution
consists of cyclic
species (RAs)n,with
n=3 (2) and n=5 (3) as
the preferred sizes.
Lloyd et al. (2005) Angewandte
Chemie 117 (6), 963.
Salvarsan
(Compound 606,Hoechst 1910)
Atoxyl
(Bechamp 1859)
Prof.Suryawanshi C.P.
16. FirstAntibiotics: Domagk Discovers Sulfonamides (“Sulfa-Drugs”)
Gerhard J. P. Domagk
(Wuppertal, 1895-1964)
Worked at Bayer (IG Farben) where
he discovered and developed
sulfonamides (Prontosil), the first
drugs effective against bacterial
infections.
Nobel Price in Medicine 1939 for
discovery of sulfonamides.
Prontosil (red azo dye)
(Bayer 1935)
Sulfanilamide
(1936)
Prontosil is a prodrug that is not active in vitro.
Cleavage in the gastrointestinal tract leads to the active
compound sulfanilamide which is competes with p-
aminobenzoic acid, the substrate of dihydropteroate
synthetase in the bacterial synthetic pathway to folic
acid.
Prof.Suryawanshi C.P.
17. First Antibiotics: Domagk Discovers Sulfonamides (“Sulfa-Drugs”)
Domagktreatedhis own daugtherwith prontosilto fight
a severestreptococcalinfectionand eventuallysaved
her life.
He was forced by the Nazi regime to refuse the Nobel Price
and was finally able to receive the price in 1947 (but not the
monetary portion).
Sulfanilamide had a central role in preventing infectionduring
WW II.
A toxic preparationof sulfanilamide in diethylene glycol(Elixir
Sulfanilamide)killed over 100 children in the US, and led to
the passage of the FederalFood,Drug,and CosmeticAct
(FD&C)by Congress in 1938 giving authority to the Food and
Drug Administration(FDA) to oversee the safetyof drugs.
Prontosil (red azo dye)
(Bayer 1935)
Sulfanilamide
(1936)
GerhardJ. P.Domagk
(Wuppertal, 1895-1964)
Worked at Bayer (IG Farben)
where he discovered and
developed sulfonamides
(Prontosil), the first drugs
effective against bacterial
infections.
Nobel Price in Medicine 1939 for
discovery of sulfonamides.
Prof.Suryawanshi C.P.
18. First Antibiotic from a Natural Source: Fleming Discovers Penicillin
AlexanderFleming(London,1881-1955)
NobelPrice in Medicine1945 for discoveryof penicillin(with Chain and Florey).
Penicillin
(R= benzyl, alkyl, etc.)
Penicillins are -lactam antibiotics that act as suicide
substrates for peptidoglycan transpeptidases involved in
crosslinking the bacterial cell wall.
AlexanderFlemingobserved, workingat St. Mary's Hospital in London in
1928, that a plate culture of Staphylococcus had been contaminatedby a
blue-greenmold (Penicillium) and that coloniesof bacteriaadjacentto the
mold were being dissolved.The mold grown in pure cultureproduced a
substancethat killedbacteria.
Naming the substance penicillin, Flemingin 1929 publishedthe resultsof his
investigations(Brit. J. Exper. Path. 1929, 10, 226).
Prof.Suryawanshi C.P.
19. First Antibiotic from a Natural Source: Fleming Discovers Penicillin
AlexanderFleming
(London, 1881-1955)
NobelPrice in Medicine1945 for
discoveryof penicillin (with Chain
and Florey).
Penicillin
(R= benzyl, alkyl, etc.)
ErnstB. Chain
(1806-1979)
Howard W. Florey
(1898-1968)
In 1939,Australian H. W.Florey,GermanE. B. Chain, and
others,working at the University of Oxford,reinvestigated
penicillin and demonstrated its in vivo efficacy(Lancet 1940,
239, 226).
They started to work on the larger scale productionof
penicillin. In 1941,laboratories at the US Departmentof
Agriculture and Merck & Co joined into penicillin research.
A high yield producing strain (Penicillium chrysogenum)
was isolated from a moldy cantaloupe that a scientist
brought to the laboratory.
Within a short period,large scale productionof pencillin
was established to produce antibiotic forthe Allied forces.
Prof.Suryawanshi C.P.
20. FirstAntibioticfroma NaturalSource: IndustrialProduction of Penicillin
Despite efforts of mass
production, availability of
penicillin was severely
limited. Rapid renal
clearance of the drug
required frequent
administration at high doses.
In the early days of
penicillin therapy it was
common practice to re-
isolate the drug from
excreted urine of patients
for reuse.
1940: priceless
1943: $20 /dose
1946: $0.55 /dose
Photos: Penicillin production in the 1940s
Prof.Suryawanshi C.P.
21. FirstAntibioticfrom a Natural Source: Penicillin& -Lactams
DorothyM.C. Hodgkin
(Oxford, 1910-1994)
NobelPrice in Chemistry1964
for X-ray crystallographic
structuredeterminationof
importantbiochemical
molecules.
In 1944, Hodgkincrystallizedpenicillinand determined its structure by X-ray crystallography, solving a
controversyaroundthe chemicalconstitutionof the antibiotic and paving the way fordiscoveryof
improved antibiotics by modificationof the natural products and total synthetic approaches.
Since then, penicillins and other -lactamdrugs have become the single most important class of
antibiotics.
Penicillins Cephalosporins
Oxacephamycins Carbapenems
Clavulanate Monobactams
Prof.Suryawanshi C.P.
23. Antibioticsfrom Systematic Screening: Waksman & Aminoglycosides
Selman A.Waksman(New Jersey,1888-1973)
Workedat Rutgers University where
he systematicallyscreened soil
bacteria and fungi as source of
antibiotics.Discovereda number of
new antibiotics,including actinomycin,
clavacin, streptothricin,streptomycin,
grisein, neomycin,fradicin, candicidin,
candidin, and others.
NobelPrice in Medicine 1952 for
discoveryof streptomycin,the first
antibiotic effectiveagainst
tuberculosis.
Streptomycin (1943)
from Streptomyces griseus
NeomycinB (1948)
from S. fradiae
Aminoglycoside antibiotics bind to the decoding regionof
bacterial ribosomalRNAand interfere with the accuracy of
proteinsynthesis.
Funded by Merck & Co, Waksmanadopted methodsof
mass screening that had beensuccessfulin the German dye
industry (also -> Salvarsan) to identifynew antibacterial
natural products.
Waksman’s laboratory performed the microbiological
screening, and Merck scientists took over chemistry,
pharmacologyand large scale production.
Prof.Suryawanshi C.P.
24. Antibioticsfrom SystematicScreening: Waksman&Aminoglycosides
Nov.1949
Two years after World War II, the two antibiotics commercially developed by Merck &
Co, penicillin and streptomycin, account for half the sales of all drugs.
Streptomycin production at Merck
in the 1940s
The Merck company
agreed to turn over the
rights for streptomycin to
Rutgers University, which
in turn licensed
companies for production.
In the late 1940s eight
pharmaceutical
companies began mass
producing streptomycin.
An estimated $1 million
worth of the drug was
provided for one the
largest clinical studies of
a drug ever undertaken, a
study involving several
thousand tuberculosis
patients.
Prof.Suryawanshi C.P.
44. β-LACTAMASE INHIBITORS
Has negligible antibacterial activity.
Given with Penicillins which increases spectrum of activity and
prevent microbial resistance to beta lactam antibiotics.
S
N
O
S
N
OH H
O
Beta-lactamse
Prof.Suryawanshi C.P.
46. • Clavulanic acid:
Isolated from Streptomyces clavuligerus.
1stnaturally occurringβ-lactam ring that was not
fused to a ‘S’ containing ring.
• Sulbactum:
β-lactamase disabiling agent.
Prepared by partial chemicalsynthesis from
penicillins.
Prof.Suryawanshi C.P.
48. 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, but it is easier to expand the ring system of 7-APA
because it is so widely produced.
• They were isolated from cultures of Cephalosporium
acremonium by italian scientist Giuseppe Brotzu in 1945.
Prof.Suryawanshi C.P.
49. • In 1948, Abraham and his colleagues have isolated three principle
antibiotic components from cultures of fungus.
cefalothin was
• 1964 ,the first semi synthetic cephalosporin i.e.
launched in the Market by Eli Lilly and company.
• Unlike penicillin, cephalosporins have two side chains which can be
easily modified. Cephalosporins are also more difficult for β-
lactamases to hydrolyze.
Cephalosporin P
Cephalosporin N
Cephalosporin C
Prof.Suryawanshi C.P.
54. 2nd Generation Cephalosporins
Theyhave a greater gram-negative
spectrum while retaining some activity
against gram-positive bacteria.
They are also more resistant
to β-lactamase.
No BBB Penetration.
Cefachlor
Cefamycin
Cefuroxime
Prof.Suryawanshi C.P.
56. 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;
different tissues, and then have broad
(e)Easy penetrate to
distribution;
(f) Little kidney toxicity.
Prof.Suryawanshi C.P.
60. Cephalosporins advantages over penicillins
Increased acid stability compare to penicillins.
Most of the drugs have better absorption than penicillins.
Broad antimicrobialspectrum.
Increased activity against resistant microorganisms.
Decreased allergenicity.
Increased tolerence than penicillins.
Prof.Suryawanshi C.P.
61. Carbapenam
• 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
carbapenem thienamycin, a
originally developed from the
naturally derived product of
Streptomyces cattleya
Examples: Imipenem, Meropenem, Ertapenem
Prof.Suryawanshi C.P.
62. IMIPENEM:
IMIPENEM has a wide spectrum with good activity many gram
negative rods incluiding P.aeruginosa, gram positive organisms
and anaerobes.
Imipenem is inactivated by dehydropeptidases in renal tubules,
result in low urinary concentrations.
Prof.Suryawanshi C.P.
63. Monobactam
aganistGram-negative rods (including Pseudomonas and Serratia).
They have no activity against Gram-positivebacteria or anaerobes.
• Examples: Aztreonam,Tigemonam.
Introduction:
Monobactams are drugs with a monocyclic β-lactam ring.
They are relatively resistant to beta-lactamases and active
Prof.Suryawanshi C.P.
64. 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)
Aztreonam
Prof.Suryawanshi C.P.
65. Introduction
✓ Antibiotics contain an aminocyclitol moiety to which
aminosugars 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
Medicinal Chemistry of Aminoglycoside Antibiotics
Prof.Suryawanshi C.P.
66. 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
Prof.Suryawanshi C.P.
67. ✓ 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
Prof.Suryawanshi C.P.
68. 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.
✓ G(+) and G(-) aerobic cocci except staphylococci and
anaerobic bacteria are less susceptible.
Prof.Suryawanshi C.P.
70. SAR of Aminoglycosides
O
O
O
O
OH
NH2
OH
H2N
OH
NH2
H2N
HO
H2N
HO
OH
1 2
3
4
5
6
1'
2'
4'
1''
3'
2''
5'
3''
5''
4''
6''
6'
I
II
III
ANT-4'
ANT-4''
ANT-2''
, APH-2''
AAC- 6'
AAC- 2'
APH- 3'
AAC- 3
Kanamycin B
✓ Ring I is very necessary for broad-spectrum
antibacterial activity.
✓ 2` and 6`-NH2 groups are specially important.
Exchanging of one of them in kanamycin B with
hydroxyl group decreases the activity ( kanamycin A, C)
Prof.Suryawanshi C.P.
71. SAR of ring I continued
✓ Methylation of C-6` or 6`- NH2 doesn’t alter the
antibacterial activity, but increases the resistance
against AAC.
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
Lack 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
Prof.Suryawanshi C.P.
72. SAR of ring I continued
✓ Omitting the 3`-OH and/or 4`-OH in kanamycin doesn’t decrease
the antibacterial activity but increases the resistance against AAC:
3`,4`-dideoxykanamycin B: Dibekacin.
The same is true for gentamicin.
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
3`-deoxy derivative
APH Resistant
4`-deoxy derivative
ANT Resistant
Prof.Suryawanshi C.P.
73. SAR of ring I continued
O
O H
H 3 C
N H C H 3
O H
O
N H R
H O
O
O
N H 2
C H 2 O H
H 2 N
1
6
2
4 3
5
1 '
2 '
3 '
4 '
1 ''
2 ''
3 ''
5 ''
4 ''
5 '
S is o m ic in : R = H
N e t ilm ic in : R = C 2 H 5
✓ Omitting the 3`-OH and 4`-OH and the addition
of a double bond between C-4` and C-5`has the
same effect.
Prof.Suryawanshi C.P.
74. SAR of Aminoglycosides continued
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, L-AHBA derivative of
Kanamycin A
C C
O
CH2 CH2 NH2
OH
H
2
2-Deoxystreptamine
Kanosamine
✓ Ring II is flexible toward changes. 1-NH2 in kanamycin can
be acylated and the antibacterial activity remains almost
unchanged , but resistance against deactivating enzymes
increases: Amikacin
Prof.Suryawanshi C.P.
75. SAR of ring II continued
✓ 1-NH2 ethylation of sisomycin saves the
antibacterial activity and increases the enzymatic
resistance: Netilmycin
O
OH
H3C
NHCH3
OH
O
NHR
HO
O
O
NH2
CH2OH
H2N
1
6
2
4 3
5
1'
2'
3'
4'
1''
2''
3''
5''
4''
5'
Sisomicin: R=H
Netilmicin: R=C2H5
Prof.Suryawanshi C.P.
76. SAR of Aminoglycosides continued
O
O
O
O
H C
N H 2
H 2 N
O H
N H
H 3C
N H 2
H O
1''
2''
3''
4''
5''
1'
2'
3'
4'
6'
5'
1
2
3
4
5 6
G arosam in e
2-D eoxystrep tam in e
G en tam icin C 1: R 1= R 2 = C H 3
G en tam icin C 2: R 1 = C H 3 ; R 2 = H
G en tam icin C 1a: R 1= R 2 = H
O H
C H 3
N H R 2
R 1
I
II
III
✓ Ring III functional groups are less sensitive to modifications:
✓ 2``-deoxy gentamicins are less active than 2``-OH ones, but 2``-
NH2 derivative (seldomycin) are very active.
✓ 3``- NH2 can be primary or secondary.
✓ 4``-OH can be axial or equatorial, the former is resistant against the
deactivating enzymes (ANT).
Prof.Suryawanshi C.P.
77. Mechanism of Action of Aminoglycosides
✓ Inhibition of protein
biosynthesis initiation upon
attachment to 30s portion of
ribosomes.
✓ Misreading mutation of the
genetic code and the synthesis
of nonesense proteins which
are not normal proteins so
they cannot take part in
cellular activities.
✓ Nonesense proteins disturb
the semipermeabilityof the
bacterial cell and
aminoglycoside molecules
enter the cell easily and kill it.
Prof.Suryawanshi C.P.
78. TherapeuticAgents
Kanamycin
O
O
O
O
R 1 H 2 C
H O
H O
R 2
H 2 N
O H
N H 2
H O H 2 C
H O
N H 2
H O
1 ''
2 ''
3 ''
4 ''
5 ''
6 ''
1 '
2 '
3 '
4 '
6 '
5 '
1
2
3
4
5 6
K a n o sa m in e
2 -D e o x y str e p ta m in e
K a n a m y c in A : R 1 = N H 2 ; R 2 = O H
K a n a m y c in B : R 1 = N H 2 ; R 2 = N H 2
K a n a m y c in C : R 1 = O H ; R 2 = N H 2
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.
Prof.Suryawanshi C.P.
80. Tobramycin
• Isolated from cultures of Streptomyces tenebrarius.
• Antimicrobial activity against resistance P.aeroginosa.
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
Prof.Suryawanshi C.P.
81. Gentamicin
✓ Isolated from cultures of Micromonospora purpurea.
✓ The suffix “micin” denotes its origin.
✓ It is used against urinary infections caused by G(-) and
pseudomona.
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
Prof.Suryawanshi C.P.
85. 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.
Prof.Suryawanshi C.P.
86. 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
Prof.Suryawanshi C.P.
88. TETRACYCLINES
INTRODUCTION :
Tetracyclic group of antibotic that include tetracycline.
Tetracyclines are obtained by fermentation From
Streptomyces spp. Or by chemical transformation of
natural products.
They are derivatives of an octahydro- naphthacene, a
hydrocarbon system that comprises four annulated six
melines is a mbre rings.
Prof.Suryawanshi C.P.
89. Mechanism of Action
Tetracyclines are specific inhibitors of bacterial
protein synthesis.
They bind to the 30S ribosomal subunit and thereby
prevent the binding of aminoacyl tRNA to the
mRNA ribosome complex.
Tetracyclines also inhibit protein synthesis in the
host but are less likely to reach the concentration
required because eukaryotic cells do not have a
tetracycline uptake mechanism.
Prof.Suryawanshi C.P.