Tetracycline
- 1. Tetracycline PRESENTED BY : P. RAJU ROLLNO :09CM1R0026 UNDER GUIDANCE OF : SUBHAS SHAOO SIR 1
- 2. CONTENTS Introduction Classificationand there structures Mechanism of action Structure Activity Relationship Spectrum of activity Toxicity and uses 2
- 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. 3
- 4. CLASSIFICATION TETRACYCLINES INTERMEDIATE SHORT ACTING: ACTING: LONG ACTING: •Tetracycline •Demeclocycline •Doxycycline •Oxytetracycline •Lymecycline •Minocycline 4
- 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. 5
- 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 6
- 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. 7
- 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. 8
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- 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. 10
- 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 11
- 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 12 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 13
- 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. 14
- 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. 15
- 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. 16
- 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. 17
- 18. Reference Text book of MEDICINAL CHEMISTRY volume-II By – K.Ilango and P.Valentine. 18
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