Tetracyclines

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Tetracyclines

  1. 1. TETRACYCLINES Presented by T.SHIVAKUMARKOTTAM INSTITUTE OF PHARMACY
  2. 2. CHEMICAL STRUCTURE OFTETRACYCLINE:
  3. 3. NOMENCLATURESystematic (IUPAC) name(4S,6S,12aS)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a- octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11- dioxonaphthacene-2-carboxamide OR(4S,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6- methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2- carboxamide
  4. 4. CHEMICALNAMEChemical Name: A variably hydrated form of (4S,4aS,5aS,6S,12aS)-4-Dimethylamino- 1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a- pentahydroxy-6-methyl-1,11-dioxonaphthacene-2- CarboxamideMolecular Formula: C22H24N2O8
  5. 5. Physical PropertiesCOLOUR: yellow crystalline powder.SOLUBOLITY: Very slightly soluble in water; soluble in alcohol and in methyl alcohol;sparingly soluble in acetone. It dissolves in dilute acid and alkaline solutions.. It loses not more than13% of its weight on drying.
  6. 6. Chemical propertiesThe reactions that tetracyclinesundergo are generally of asophisticated nature, dictated by thecomplex functionality and thesensitivity of the molecules to mildreaction conditions (acid, base, heat) .
  7. 7. Acidic conditions The conjugated triones system extending from C1 to C3 of ring A is acidic in nature with PKa1=2.8 to 3.4. When exposed to dilute acid conditions, tetracycline undergoes dehydration to yield anhydrotetracycline. Anhydroterramycin suffers further cleavage and lactonization to apoterramycin:Diluted acid promotes epimerization at C-4 as well.
  8. 8. Basic conditions C4 atom and its substitute exhibits PKa2ranging from 9.1 to 9.7 which representsstrong alkaline natureMild alkali attacks 11a carbon oftetracycline, which is transformed toisotetracycline
  9. 9. The reasons for ammphoteric nature of tetracyclines is their complex structure with three structural units representing three PKa values. The conjugate phenolic enone system from C10 to C12 is associated with weak basic PKa values ranging from 7.2 to 7.8.
  10. 10. Because of the amphoteric nature, tetracyclines are capable of forming water-sluble salts with strong acids such as hydrochloric acid and strong bases such as sodium hydroxide and potassium hydroxide.And water insoluble salts of tetracyclines are formed with divalent and polyvalent metals
  11. 11. INCOMPATIBILITY: Chelation with metals: among the chemical and clinical properties of tetracyclins, chelation with ions is an important feature.Tetracyclins are able to form complexes with divalent and trivalent metal ions such as Fe3+, Fe2+, Cu2+, Ni2+, Co2+, Zn2+, Mn2+, Mg2+, Ca2+, Be2+, Al3+ and with salicilates, phosphates,citrates,polyvinylprrolidine,t hiourea,lipoproteins,serum albumin,globulin and RNA.
  12. 12. These salts of metal ions are insoluble in water atneutral conditions and cause inconvenience in theprepararion of solutions and also produceunfavourable blood titres of tetracyclines, within thebody
  13. 13. STBILITY :EPIMERISATION: One of the important property of tetracycline is their ability to undergo epimerization at C4 position and the isomers are referred to as epitetracyclines.
  14. 14. CLASSIFICTION OF TETRACYCLINS :According to source:Naturally occurringTETRACYCLINECHLORTETRACYCLINEOXYTETRACYCLINEDEMOCYCLINE
  15. 15. Semi-synthetic Doxycycline Lymecycline Meclocycline Methacycline MinocyclineRolitetracycline
  16. 16. According to duration ofaction:Short-acting (Half-life is 6-8 hrs) Tetracycline Chlortetracycline Oxytetracycline
  17. 17. Intermediate-acting (Half-life is ~12 hrs) 1.Demeclocycline 2.Methacycline Long-acting (Half-life is 16 hrs or more) 1.Doxycycline 2.Minocycline 3. Tigecycline
  18. 18. REFERENCESBurden, V. (1991). Purification and characterizationof tet(M), a protein that renders ribosomes resistantto tetracycline. Journal of Biological Chemistry 266,2872-7 .Chaudhary, I., Wirth, M., Rosen, R., Nicolau, G. & Yacobi, A. (1993). Metabolism of DMGDMDOTa novel antibiotic in laboratory animals, in vitro/in vivo correlations.Chopra, I., Hawkey, P. M. & Hinton, M. (1992). Tetracyclines, molecular and clinical aspects.Journal of Antimicrobial Chemotherapy 29,245-77.Eliopoulos, G. M., Wennersten, C. B., Cole, G.& Moellering, R. C. (1994). In vitro activities of
  19. 19. Thank you….T.SHIVASHIVA.PHARMACIST@GMAIL.COM

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