Tetracyclines are a class of antibiotics with a yellow crystalline powder appearance. They are slightly soluble in water but more soluble in alcohol, methyl alcohol, acetone, and dilute acids or bases. Tetracyclines undergo reactions dictated by their complex structure, being sensitive to mild acidic and basic conditions. They can form both water-soluble and insoluble salts. Tetracyclines also chelate with metal ions, forming insoluble complexes that reduce their bioavailability. They are classified based on their source as natural, semi-synthetic, or duration of action.

1. TETRACYCLINES
Presented by
T.SHIVAKUMAR
KOTTAM INSTITUTE OF
PHARMACY

2. CHEMICAL STRUCTURE OF
TETRACYCLINE:

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. 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. 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.

6. 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) .

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. 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

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. 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. 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. 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

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. CLASSIFICTION OF
TETRACYCLINS :
According to source:
Naturally occurring
TETRACYCLINE
CHLORTETRACYCLINE
OXYTETRACYCLINE
DEMOCYCLINE

15. Semi-synthetic
Doxycycline
Lymecycline
Meclocycline
Methacycline
Minocycline
Rolitetracycline

16. According to duration of
action:
Short-acting (Half-life is 6-8 hrs)
Tetracycline
Chlortetracycline
Oxytetracycline

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. 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. Thank you….T.SHIVA
SHIVA.PHARMACIST@GMAIL.COM