Biomedical Engineering Reference
In-Depth Information
compounds were evaluated for their relaxant potency in rat aorta and trachea. The
chemical space of the compounds was parameterized using the Log
P
, heat of
formation, ionization potential, dipole moment, HOMO, LUMO, electronegativity,
hardness, polarity and GRID based 3D-interaction energy maps [
37
]. The models
were derived using principal component analysis (PCA) and partial least-squares
(PLS) analysis. A 3-component PLS model has explained 81 and 82% variance,
respectively, in the aortic and the tracheal responses of the compounds. The models
have suggested a direct bearing of 6-substituents on the receptor site, presumably
via dipolar interactions. Apart from this, electronegativity, heat of formation,
substituent size, lipophilicity, low minimum energies were identified as the domi-
nant molecular properties in the PLS components in explaining the biological
response of these compounds [
37
].
N
O
R
O
3
In an attempt to offer simpler QSAR models, Agrawal et al. [
38
] have
reinvestigated Mannhold et al.'s data [
37
] in stepwise regression with distance-
based topological indices, negentropy and molecular redundancy indices. This has
resulted in the following 4-parameter model to explain the relaxant activity (rat
trachea; EC
50
) of the compounds.
pEC
50
¼
1
:
4982
þ
3
:
7015
ð
0
:
9099
Þ
J
þ
5
:
2400
ð
1
:
8987
Þ
MRI
W
10
4
10
4
þ
2
:
1840
1
:
7955
1
:
2294
ð
0
:
1522
Þ
I
p
1
n
¼
28
;
r
¼
0
:
9406
;
s
¼
0
:
3254
;
F
¼
44
:
143
:
(2)
In this equation,
J
is distance-based topological index, MRI is molecular infor-
mation content,
W
is Wiener index and
I
p
1
is an indicator parameter. The negative
coefficient of
I
p
1
suggested that 'oxy' substitution at R (6-position) is not favorable
for the activity. The positive regression coefficients of
J
, MRI and
W
indicated that
an increased information content of these descriptors can improve the activity [
38
].
Even though some information is lost fromMannhold et al.'s model, Agrawal et al.'s
attempt has offered much simpler rationale for the activity of the compounds.
2.2.2
4,6-Disubstituted-2,2-Dimethylchroman Derivatives
The PCOs have definite role in insulin secretion from the pancreas. Cromakalim
provokes the relaxation of smooth muscles and/or the inhibition of endocrine
