Biomedical Engineering Reference
In-Depth Information
a molecule. A lower value for these descriptors is required to improve the
myorelaxant activity. The descriptors X2A and PW3 represent topological class.
The X2A is the average connectivity index chi-2. It encodes information about size,
branching, cyclization, unsaturation and heteroatom content in a molecule. Small
value for this descriptor would enhance the activity. The PW3 is path/walk Randic
shape index of order 3. A higher value of this index would be beneficiary to the
activity. The C-040 represents the count of structural fragments having carbon
atoms attached to the hetero atom by single or multiple bonding and one valence
is satisfied by an alkyl group [R-C(=X)-X
0
/ R-C#X where X and X
0
are heteroatoms,
and -, = and # represent single, double and triple bonds, respectively]. In the
molecules, a structural feature of this kind is helpful in augmenting the activity.
Collectively, all these observations provided the detailed structural requirements
in these compounds (4) for the myorelaxant activity.
2.2.3 Chromanol Derivatives
Chromanols (5) are closely related to cromakalim and inspired the researchers to
explore them as potential K
ATP
-channel blockers. Gerlach et al. investigated them for
their potassium channel blocking activity (IC
50
) using human
I
Ks
channel expressed
in
Xenopus oocytes
[
45
]. The R
1
in these analogues is either methyl, ethyl, or butyl
group. The
O
R
1
S
O
X
OH
O
5
X-substituent on the aryl moiety has variations in terms of CN, F, Cl and alkoxy
groups. Gupta et al. [
46
] discovered following elegant linear models for the
potassium channel blocking activity of these analogues in terms of the hydrophobic
constant of X-substituent and indicator parameters
I
CN
and
I
Cf
.
log 1
ð
=
IC
50
Þ¼
5
:
441
ð
0
:
263
Þ þ
0
:
760
ð
0
:
226
Þp
X
(6)
n
¼
17
;
r
¼
0
:
880
;
s
¼
0
:
42
;
F
¼
51
:
53
:
log 1
ð
=
IC
50
Þ¼
5
:
642
ð
0
:
268
Þ þ
0
:
514
ð
0
:
203
Þp
X
0
:
732
ð
0
:
453
Þ
I
CN
þ
0
:
585
ð
0
:
312
Þ
I
Cf
(7)
Q
2
n
¼
17
;
r
¼
0
:
961
;
¼
0
:
87
;
s
¼
0
:
26
;
F
¼
52
:
80
:
Equations (6) and (7) clearly indicated the favorable role of hydrophobicity for
the activity. In (7), the parameter
I
CN
was assigned a value of 1 for X
¼
CN and the
