Biomedical Engineering Reference
In-Depth Information
releases [
39
,
40
]. However, cromakalim is poorly active as an inhibitor of insulin
secretion [
41
,
42
]. Therefore, in order to discover potent pancreatic
-cell selective
PCOs, Sebille et al. [
43
] synthesized 4,6-disubstituted-2,2-dimethylchromans (4),
structurally related to cromakalim, and evaluated them for insulin secretion from rat
pancreatic islets and on the contractile activity of rat aorta rings.
b
H
N
R
2
R
1
O
4
In an attempt to rationalize the activity of these compounds (4), Sharma et al.
[
44
] have carried out a QSAR study with CP-MLR feature selection approach for
optimum models. This study has identified following equations for the contractile
activity of KCl-depolarized rat aorta rings (pED
50
, where ED
50
is the concentration
in moles per liter for 50% inhibition against the K
ATP
channel) of the compounds.
pED
50
¼
60
:
747
55
:
466 12
ð
:
333
Þ
MATS4m
þ
12
:
837 2
ð
:
649
Þ
MATS1p
þ
0
:
598 0
ð
:
141
Þ
C
040
(3)
Q
2
n
¼
25
;
r
¼
0
:
876
;
¼
0
:
672
;
s
¼
0
:
338
;
F
¼
23
:
072
:
pED
50
¼
24
:
913
65
:
976 10
ð
:
109
Þ
X2
A
2
:
207 0
ð
:
499
Þ
GGI7
þ
7
:
881 1
ð
:
724
Þ
MATS4p
(4)
Q
2
n
¼
25
;
r
¼
0
:
872
;
¼
0
:
672
;
s
¼
0
:
343
;
F
¼
22
:
287
:
pED
50
¼
5
:
694
þ
31
:
396 5
ð
:
011
Þ
PW3
3
:
111 0
ð
:
678
Þ
GGI8
þ
10
:
219 2
ð
:
501
Þ
MATS1p
þ
1
:
330 0
ð
:
585
Þ
GATS5p
(5)
Q
2
n
¼
;
r
¼
:
;
¼
:
;
s
¼
:
;
F
¼
:
:
25
0
899
0
722
0
314
21
076
In these equations, MATS1p, MATS4p, MATS4m and GATS5p are 2D auto-
correlation descriptors [
23
]. MATS1p and MATS4p are the Moran autocorrelation
of topological structure with path length (
lag
) 2 and 4, respectively, in the graph
weighted by atomic polarizabilities. GATS5p is the Geary autocorrelation of
lag
5
weighted by atomic polarizabilities. The regression coefficients of these descriptors
indicate that the higher path lengths rich in polarizability content would be favor-
able for the improvement of activity. The descriptor MATS4m is Moran autocorre-
lation of
lag
4 in the graph weighted by atomic masses. The negative regression
coefficient associated with this descriptor suggests that a lower path length rich in
atomic mass would be beneficial. The descriptors GGI7 and GGI8 are Galvez
topological charge indices of orders 7 and 8, respectively. They represent the
seventh and eighth eigenvalues, respectively, of the corrected adjacency matrix of
