tetracyclins

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TETRACYCLINES

• Presented by
• T.SHIVAKUMAR
• KOTTAM INSTITUTE OF PHARMACY

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CHEMICAL STRUCTURE OF TETRACYCLINE
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NOMENCLATURE

• Systematic (IUPAC) name
• (4S,6S,12aS)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12
  a-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-penta
  hydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-o
  ctahydrotetracene-2-carboxamide

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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-pe
  ntahydroxy-6-methyl-1,11-dioxonaphthacene-2-
• Carboxamide
• Molecular Formula C22H24N2O8

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Physical Properties
COLOUR 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.
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Chemical properties

• The reactions that tetracyclines undergo are
  generally of a sophisticated nature, dictated by
  the complex functionality and the sensitivity of
  the molecules to mild reaction conditions (acid,
  base, heat) .

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Acidic conditions 

• The conjugated triones system extending from C1
  to C3 of ring A is acidic in nature with PKa12.8
  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.

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• Basic conditions C4 atom and
  its substitute exhibits PKa2 ranging from 9.1 to
  9.7 which represents strong alkaline nature
• Mild alkali attacks 11a carbon of
  tetracycline, which is transformed to
  isotetracycline

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Amphoteric nature

• 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.

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• 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

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• 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,thiourea,l
  ipoproteins,serum albumin,globulin and RNA.

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These salts of metal ions are insoluble in water
at neutral conditions and cause inconvenience in
the prepararion of solutions and also produce
unfavourable blood titres of tetracyclines,
within the body
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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.

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CLASSIFICTION OF TETRACYCLINS

• According to source
• Naturally occurring
• TETRACYCLINE
• CHLORTETRACYCLINE
• OXYTETRACYCLINE
• DEMOCYCLINE

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Semi-synthetic

• Doxycycline
• Lymecycline
• Meclocycline
• Methacycline
• Minocycline
• Rolitetracycline

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According to duration of action

• Short-acting (Half-life is 6-8 hrs)
• Tetracycline
• Chlortetracycline
• Oxytetracycline

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Intermediate-acting (Half-life is 12
hrs)1.Demeclocycline2.Methacycline
Long-acting (Half-life is 16 hrs or more)
1.Doxycycline2.Minocycline3.Tigecycline
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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

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• Thank you.T.SHIVA
• 
  SHIVA.PHARMACIST_at_GMAIL.COM