tetracyclines

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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