This document discusses the antibiotic tetracycline. It belongs to a group of antibiotics called tetracyclines which are obtained through fermentation of Streptomyces bacteria. Tetracycline has a complex stereochemistry and exists as a zwitterion. It works by inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit. It is stable under acidic conditions but forms anhydrotetracycline, while under basic conditions it opens to form isotetracycline. It forms insoluble chelates with metals. Tetracycline has broad-spectrum activity against many gram-positive and gram-negative bacteria.

1. Tetracycline
PRESENTED BY : P. RAJU
ROLLNO :09CM1R0026
UNDER GUIDANCE OF : SUBHAS SHAOO
SIR
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2. CONTENTS
 Introduction
 Classificationand there structures
 Mechanism of action
 Structure Activity Relationship
 Spectrum of activity
 Toxicity and uses
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3. INTRODUCTION
 Tetracyclines is a 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 membre rings.
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4. CLASSIFICATION
TETRACYCLINES
INTERMEDIATE
SHORT ACTING: ACTING:
LONG ACTING:
•Tetracycline •Demeclocycline
•Doxycycline
•Oxytetracycline •Lymecycline
•Minocycline
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5. Structure Of Tetracycline
 The stereochemistry of the tetracycline is very complex.
carbon atom 4,4a,5,5a,6 and 12a, are potentially chiral
depending on substitution.
 Oxytetracycline and Doxycycline posses 5alpha-hydroxy
substituent have six chiral carbon and others have five
chiral carbon.
 These are amphoteric compounds, forming salts with
either acids or bases.
 It exists mainly as zwitter ions in neutral solutions .
 They are yellow in colour , The HCL salts are used for
oral adminstration and usually given in the form of
capsule to mask the bitter taste.
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6. STRUCTURE OF TETRACYCLINES
H N
O 2
HO O R4 R3 R2 R1 N
R3 R2 H
R4 R1 4 OH
OH 8 7 6 5
H CH BH OH 3
H 9 D A 2
N 10 11 12 1 CONH 2
O OH H
OH O OH O
OH
ÍÁùËØ Oxytetracycline£©
£¨ R1 = -OH R2 = -OH R3 = -CH3 R4 = -H
½ð
ùËØ Chlotetracycline£©
£¨ R1 = -H R2 = -OH R3 = -CH3 R4 = -Cl
ËÄ ËØ Tetracycline£©
»· £¨ R1 = -H R2 = -OH R3 = -CH3 R4 = -H
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7. Tetracycline pharmacophore and
numbering
 Positions at the “bottom”
of the molecule (10, 11,
1) and most of ring A
(positions 2, 3, and 4)
represent the invariant
pharmacophore region of
the molecule, where
modifications are not
tolerated without loss of
antibiotic activity.
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8. 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.
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9. 9

10. SAR of tetracyclines
N(CH3)2
OH
7 5 4
6 3
8 OH
H H OH
2
9
10 11 12 1 CONH2
OH O OH O
 6-methyl-4-(dimethylamino)-3,6,10,12,12a-
pentahydroxy-1,4,4a,5,5a,6,11,12a- octahydro-
2- naphthacenecarboxamide.
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11. Stability under acid condition
 Thee tetracycline molecule, as well as those that contain
the 6β- hydroxy group, is labile to acid and base
degradation. At pH <2.0, tetracycline eliminates a
molecule of water with concomitant aromatization of ring
C to form anhydrotetracycline.
OH N OH2+ N
OH OH
OH H+ OH - H2O
H H H H
CONH 2 CONH 2
OH O OH O OH O OH O
N N
+ OH OH
OH - H+ OH
H H H
CONH2 CONH2
OH O OH O OH OH O O
ÍÑË®
Îï
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12. Formation of 4-Epitetracycline
 C-4 in At acidic medium (pH 2-6), epimerization
of the “natural” C-4 α-dimethylamino group to
the C-4β-epimer occurs. Under acidic
conditions, a 1:2 equilibrium is established in
solution within a day.
OH N OH H+N
OH OH
OH H OH
H H H
CONH 2 CONH 2
OH O OH O OH O OH OH
OH N OH N
O OH
H H OH H OH
H
CONH 2 CONH 2
OH O OH OH OH O OH O
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4-Epitetracycline

13. Stability under base condition
 In basic medium, ring C of tetracycline is opened
to form isotetracycline.
OH N O- N
OH OH
OH OH - OH
H H H
CONH 2 CONH 2
OH O OH O OH O OH O
N N N
H H
OH OH OH
OH OH OH OH
O O
CONH 2 CONH 2 CONH 2
- O O O- O O O O
OH O O OH OH
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14. Formation of metal chelates
OH N(CH3)2
OH N(CH3)2
Mn+ OH
OH
H H OH
H H OH
CONH2
CONH2
OH O O O
OH O OH O
Mn+
 Stable chelate complexes are formed by the tetracycline
with many metals, including , calcium,magnesium and
iron. Such chelates are usually insoluble in water.
• The tetracyclines are distributed into the milk of lactating
mothers and will cross the placental barrier into the
fetus.
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15. Spectrum of activity
 Tetracyclines are broad spectrum
antibiotics, active against wide range of
Gram-positive and Gram-negative
bacteria, spirochetes, mycoplasm,
rickettsiae, and chalmydiae.
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16. Toxicity of tetracycline
 Use of this medication for prolonged or repeated
periods may result in oral thrush or a new yeast
infection (oral or vaginal fungal infection).
 Nausea, vomiting, diarrhea, loss of appetite,
mouth sores, black hairy tongue, sore throat
, dizziness, headache, or rectal discomfort may
occur.
 This antibiotic treats only bacterial infections. It
will not work for viral infections (e.g.,common
cold, flu). Unnecessary use or overuse of any
antibiotic can lead to its decreased
effectiveness.
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17. Uses of tetracycline
 Tetracycline is used to treat a wide variety
of infections, including acne. It is an
antibiotic that works by stopping the
growth of bacteria.
 Used in treatment of infections like
septicemia, endocarditis , meningitis.
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18. Reference
 Text
book of MEDICINAL CHEMISTRY
volume-II By – K.Ilango and
P.Valentine.
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