Biomedical Engineering Reference
In-Depth Information
model are indicative of the role for atomic mass (
m
) and the Sanderson atomic
electronegativity (
e
) in electron diffraction signals. Unweighted 3D-MoRSE elec-
tron diffraction signal number 24 (Mor24u) and atomic mass weighted 4th signal
(Mor04m) contributed negatively to the activity, whereas atomic mass weighted
10th signal (Mor10m) and Sanderson atomic electronegativity weighted 13th signal
contributed positively to the activity.
The G3u (3rd component symmetry directional WHIM index/unweighted) and
L1m(1st component size directional WHIM index/weighted by atomic masses)
belong to WHIM (weighted holistic invariant molecular descriptors) class
descriptors. They are geometrical descriptors based on statistical indices, calculated
on the projections of the atoms along principal axes. These descriptors are built in
such a way as to capture relevant molecular 3D information regarding molecular
size, shape, symmetry and atom distribution with respect to invariant reference
frames. Calculation of WHIM descriptors involves the eigenvalues of the weighted
covariance matrix of the molecular atomic coordinates. Each eigenvalue represents
a dispersion measure (i.e., the weighted variance) of the projected atoms along the
considered principal axis, thus accounting for the molecular size along that prin-
cipal direction. They describe the molecular shape. Interpretability of these
descriptors is relatively complex but they encode refined structural information
for the activity.
2.5 Khellinone Derivatives
The voltage-gated potassium channel Kv1.3 is linked with the activation of human
T cells and therefore pursued as an important target in the treatment of T-cell-
mediated autoimmune diseases such as multiple sclerosis [
58
-
60
]. Khellinone (10;
R
1
¼
Me), a naturally occurring benzofuran derivative isolated from
Ammi
visnaga
, weakly blocks Kv1.3 with an EC
50
of 45
R
2
¼
m
M[
61
]. In this background,
Baell and coworkers prepared
O
OR
2
H
3
C
O
HO
OR
1
10
a variety of khellinone derivatives as promising Kv1.3-blockers [
61
,
62
]. The
effectiveness of the compounds in blocking Kv1.3 was assayed on L929 cells stably
expressing mKV1.3. Keeping the importance of these derivatives in view, Gupta
and coworkers [
46
,
63
] attempted to rationalize the potassium channel (Kv1.3)
blocking activity of these compounds with the physicochemical and steric
parameters. For 4,7-alkoxy khellinone derivatives (10)[
62
], the Kv1.3 channel
