Biomedical Engineering Reference
In-Depth Information
blocking activity (EC
50
) was reported to be correlated with the sum of hydrophobic
constants of R
1
- and R
2
-substituents (
Sp
) and the surface tension parameter st of the
whole molecule (16) [
46
].
2
ð
=
Þ¼
:
ð
:
Þ þ
:
ð
:
ÞSp
:
ð
:
ÞðSpÞ
log 1
EC
50
3
178
2
544
2
661
0
851
0
541
0
171
þ
0
:
119
ð
0
:
041
Þ
st
Q
2
n
¼
12
;
r
¼
0
:
942
;
¼
0
:
67
;
s
¼
0
:
14
;
F
¼
20
:
86
; Sp
o
¼
2
:
46
:
(16)
has suggested 2.46 as the
optimum value for hydrophobic property of R
1
- and R
2
-substituents (
In this equation, the second-degree term in
Sp
2.46).
The equation has suggested that hydrophobicity and surface tension are important
properties for the potassium channel blocking activity of the compounds.
The khellinone derivatives shown in 11a and 11b are closely related positional
isomers of each other. They were formed by replacing the 4- and 7-alkoxy groups of
khellinone with substituted benzyloxy groups [
62
].
Sp
o
¼
O
OMe
R
H
3
C
O
HO
O
O
O
H
3
C
O
HO
R
OMe
11a
11b
Satuluri et al. [
46
] correlated the Kv1.3 channel blocking activity of these
derivatives with the Verloop's STERIMOL parameters
B
1
(minimum width of the
substituent) and
L
(length) and indicator variables as shown by (17) and (18) for 11a
and 11b, respectively.
log 1
ð
=
EC
50
Þ¼
5
:
205
ð
0
:
665
Þ þ
0
:
696
ð
0
:
392
Þ
B
1
0
:
137
ð
0
:
061
Þ
L
þ
0
:
290
ð
0
:
186
Þ
I
P
(17)
Q
2
n
¼
19
;
r
¼
0
:
852
;
¼
0
:
43
;
s
¼
0
:
17
;
F
¼
13
:
20
:
log 1
=
EC
50
ð
Þ¼
5
:
111
ð
0
:
811
Þ þ
1
:
001
ð
0
:
453
Þ
B
1
0
:
173
ð
0
:
064
Þ
L
0
:
325
0258
ð
Þ
I
O
(18)
Q
2
n
¼
16
;
r
¼
0
:
915
;
¼
0
:
71
;
s
¼
0
:
17
;
F
¼
20
:
58
:
These equations suggested that the width parameter B
1
is favorable for the
potassium channel blocking activity of the compounds. However, the negative
