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2
α
2.23
37.8
1.85
32.1
1.97
30.4
β
2.32
1.47
1.62
3
α
–
211.4
3.60
71.8
3.80
79.2
4
α
2.04
44.3
1.64
38.8
1.82
35.3
β
2.21
1.36
1.41
5
α
1.45
46.1
1.21
45.8
1.20
45.6
6
α
1.37
28.6
1.44
30.0
1.47
30.0
β
1.23
1.35
1.38
7
α
1.03
27.0
1.20
28.7
1.20
28.8
β
1.96
2.13
2.13
8
β
1.52
41.2
1.68
42.6
1.68
42.6
9
α
0.95
49.1
1.07
51.1
1.07
51.1
10
–
35.7
–
36.9
–
37.0
11
α
1.48
21.2
1.63
22.3
1.62
22.3
β
1.30
1.38
1.38
12
α
1.32
39.4
1.56
40.9
1.56
40.9
β
1.45
1.56
1.56
13
–
49.5
–
51.0
–
51.0
Cardiac Glycosides in Medicinal Plants
http://dx.doi.org/10.5772/65963
37

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A
B
C
1
H
13
C
1
H
13
C
1
H
13
C
14
–
84.7
–
86.3
–
86.3
15
α
1.98
32.7
2.20
33.4
2.20
33.4
β
1.63
1.79
1.80
16
α
2.07
26.7
2.23
28.0
2.23
28.0
β
1.79
1.95
1.95
17
α
2.72
50.7
2.91
52.1
2.90
52.1
18
0.84
15.7
0.97
16.4
0.97
16.4
19
a
0.94
11.2
0.91
12.6
0.92
12.6
b
–
–
–
20
–
174.8
–
178.4
–
178.4
21
a
4.76
73.3
5.01
75.3
5.00
75.4
b
4.95
5.11
5.12
22
5.81
117.4
5.98
117.8
5.98
117.8
23
–
174.4
–
177.2
–
177.3
1
′
4.47 (7.8)
102.3
2
′
3.22 (8.8)
75.2
3
′
3.43 (8.8)
78.1
4
′
3.35 (9.6)
71.7
5
′
3.35 (5.1;1.5)
77.9
6
′
a
3.73 (11.9;5.1)
62.8
b
3.93 (11.9,1.5)
Table 2. 
1
H and 
13
C NMR chemical shifts and characteristic 
J
(H,H) couplings of three cardenolides 
A
–
C
.
Figure 7. 
Stereostructure of 
B
. The arrows indicate steric proximities (from ROESY experiment).
Aromatic and Medicinal Plants - Back to Nature
38

---

Figure 8. 
Relative orientation of the aglycone and the sugar moiety in 
C
. The arrows refer to spatial proximities
obtained from ROESY.
7. Pharmacological action of cardiac glycosides
The most important use of the cardiac glycosides is its effects in treatment of cardiac failure.
In cardiac failure, or congestive heart failure, heart cannot pump sufficient blood to maintain
body needs. During each heart contraction, there is an influx of Na
+
and an outflow of K
+
.
Before the next contraction, Na
+
, K
+
‐ATPase must reestablish the concentration gradient
pumping Na
+
into the cell against a concentration gradient. This process requires energy,
which is obtained from hydrolysis of ATP to ADP by Na
+
, K
+
‐ATPase. Cardiac glycosides
inhibit Na
+
, K
+
‐ATPase, and consequently increase the force of myocardial contraction [8]. On
the other hand, some cardiac glycosides were investigated for their antitumor activity [61].
In addition, it has been reported that some cardiac glycosides display an inhibitory activity
against rhinovirus [62].
8. Structure-activity relationship
In cardenolides, the steroidal part is considered the pharmacophoric moiety, responsible for
the activity of these compounds [63]. Specifically, the 5β,14β‐androstane‐3β,14‐diol skeleton
has shown the same binding properties to the enzyme as digitalis compounds.
Furthermore, the bending in the structure as shown in 
cis
junctions between A/B and C/D rings
is very important to get the highest interaction energy. Any modification of A and/or B rings
related to B‐C plane, reduces the interaction energy [64]. In general, OH groups at any position
of steroidal skeleton reduce the interaction energy, which depends on the position on the
skeleton and the spatial location. This fact may be explained by the steric hindrance and the
decreasing of steroidal positive potential field. Moreover, the OH group at position C14β is
not an essential feature for inotropic activity, although when it is replaced by hydrogen atom,
potency decreases considerably [65]. The change of the A/B junction does not mean a decrease
of activity of aglycones but it decreases the activity of the corresponding glycosides. Thus, the
Cardiac Glycosides in Medicinal Plants
http://dx.doi.org/10.5772/65963
39

---

main effect of A/B junction is revealed from its ability to put the sugar into its suitable position
[66]. The lactone ring at C17β has been considered to be responsible for inotropic activity,
bringing about conformational changes on the enzyme that would give rise to its inhibition
[67]. Indeed, that is the most differentiating feature from steroid hormones, and its contribution
to the interaction [68]. Sugar attachment to the steroid part modifies both pharmacokinetics as
well as pharmacodynamics of digitalis glycosides. Free aglycones are absorbed faster than
glycosides and they are easily metabolized to less active 3α‐OH epimer. Thus, the action of
free aglycone is fast and short lasting. The sugar moiety significance for digitalis activity is
well established but sugar parts themselves do not show any activity [10].