This ppt gives a brief overview about Natural Glycosides, their classification & recent researches related to therapeutic potential of Cardiac glycosides.
2. What are Glycosides ?
Glycosides are organic molecules which consist of a sugar residue covalently
bound to a different structure called the aglycone.
The sugar residue is in its cyclic form and the point of attachment is the
hydroxyl group (sugar) of the hemiacetal (aglycone) function.
The sugar moiety can be joined to the aglycone in various ways:
1. Oxygen (O-glycoside)
2. Sulphur (S-glycoside)
3. Nitrogen (N-glycoside)
4. Carbon (C-glycoside)
Bitter in taste
Used as a defensive mechanism against predators by many plant species.
3. Classification of Glycosides
Glycosides can be classified by the glycone, by the type of glycosidic bond, and by the aglycone.
I. By glycone/presence of sugar
If the glycone group of a glycoside is
glucose, then the molecule is a glucoside;
if it is fructose, then the molecule is a fructoside;
if it is glucuronic acid, then the molecule is a glucuronide; etc. & so on
II. By type of glycosidic bond
Depending on whether the glycosidic bond lies "below" or "above" the plane of the cyclic
sugar molecule, glycosides are classified as α-glycosides or β-glycosides.
There are four type of linkages present between glycone and aglycone:
C-linkage/glycosidic bond, "nonhydrolysable by acids or enzymes"
O-linkage/glycosidic bond
N-linkage/glycosidic bond
S-linkage/glycosidic bond
4. BY AGLYCONE
Glycosides are also classified according to the chemical nature of the aglycone. For purposes of
biochemistry and pharmacology, this is the most useful classification.
Alcoholic glycosides – Eg. Salicin (converted to Salicyclic acid in the body)
Responsible for antipyretic & anti-inflammatory effects.
Anthraquinone glycosides- Eg. Antron & Anthranol
Responsible for laxative effect.
5. Cyanogenic glycosides – eg. Amygdalin
Aglycone part is cyanide.
Used as a defensive mechanism by certain plants against predators.
Flavonoid glycosides – Eg. Rutin, naringin
Responsible for Antioxidant effect, improves capillary strength.
Others include Saponins, Phenolic glycosides etc.
6. Major plant sources of Cardiac Glycosides
Scrophulariaceae
Digitalis purpurea leaves (foxglove)
Digitalis lanata leaves – white flowers
Apocyanaceae
Strophanthus vine seeds – Africa
Liliceae
Urginea bulbs (squill) – Europe, India
Convallaria leaves (lily of the valley)
7. Cardiac glycosides as potential
Anticancer agents
In a recent paper published (2013) in Oncogene journal , Tailler et
al. Identified the cardiac glycoside ouabain as a potential
antileukemic compound.
They observed that ouabain was highly efficient in inhibiting the
growth of human acute myeloid leukemia cells xenotransplanted in
immunodeficient mice, without exerting significant toxicity on the
host.
8. Mechanism of Action
It disrupts the cell sodium-Potassium ion balance. Increased
cellular levels of Na+ & Ca+ causing malfunctioning in cell
signalling processes, ultimately forcing the cancerous cell to
enter Apoptosis.
The authors concluded that ouabain was a promising
antileukemic agent whose activity should be evaluated in
prospective clinical studies
9. Another research group headed by Dr. Jose Manuel reported in 2013 that
cardiac glycosides digitoxin & digoxin and induce selective killing of lung
cancer cells, and that the cytotoxicity of digitoxin against these cells occurs
at concentrations below those observed in the plasma of cardiac patients
treated with this drug.
It has been proposed that the inhibition of the Na+/K+-ATPase pump would
decrease glycolysis activity via inhibition of the key glycolytic enzyme
phosphofructokinase. In addition, inhibition of the Na+/K+-ATPase pump may
restrict the activity of sodium glucose transporters (SGLTs), which couple
glucose entry into some types of cells with the activity of this pump.
Published paper- Oncogene, 2013. doi: 10.1038/onc.2013.229
Many other glycosidic molecules are being extensively researched as
potential therapeutics for various cardiac & cancerous diseases.
10. References
Rahimtoola, S.H. and Tak, T. The use of digitalis in heart failure Curr. Probl. Cardiol. 1996, 21, 781-
853.
Xie, Z. and Askari, A. Na(+)/K(+)-ATPase as a signal transducer Eur. J. Biochem. 2002, 269, 2434-9.
Schoner, W. and Scheiner-Bobis, G. Endogenous and exogenous cardiac glycosides: their roles in
hypertension, salt metabolism, and cell growth Am. J. Physiol Cell Physiol. 2007, 293, C509-C536.
Haux, J. Digitoxin is a potential anticancer agent for several types of cancer Med. Hypotheses. 1999,
53, 543-8.
Lopez-Lazaro, M. Digitoxin as an anticancer agent with selectivity for cancer cells: possible
mechanisms involved Expert. Opin. Ther. Targets. 2007, 11, 1043-53.
Newman, R.A.; Yang, P.; Pawlus, A.D.; Block, K.I. Cardiac glycosides as novel cancer therapeutic
agents Mol. Interv. 2008, 8, 36-49.
Prassas, I. and Diamandis, E.P. Novel therapeutic applications of cardiac glycosides Nat. Rev. Drug
Discov. 2008, 7, 926-35.