Biomedical Engineering Reference
In-Depth Information
(a) Rotlbonds is a structural descriptor and indicates number of rotational bonds in a
compound. The molecular activity and the number of rotatable bonds in the studied
compounds can be broadly correlated, and this descriptor showed positive correla-
tion with NCC blocking activity in QSAR model. On the basis of number of
rotatable bonds, the “Opera” rule needs to be specified, which in turn contribute
to the structural flexibility of the compound required for attaining bioactive confor-
mation for drug-like compounds [
78
]. (b) Thermodynamic descriptor, Atype_C_24
is one of the atom types AlogP descriptor that appeared in QSAR model. In this
descriptor, the C atom in the compound is linked in R- -CR- -R manner, where
R represents any group linked through carbon and “- -” represents aromatic bonds
as in benzene or delocalized bonds like the N-O bond of a nitro group [
79
,
80
].
Atype descriptors are thermodynamic descriptors defining the presence of that type
of atom in the compound. Various atom type AlogP descriptors can be used to
calculate the logP of compounds. In this strategy, halogens and hydrogen are
classified according to the hybridization and oxidation state of the carbon to
which they are bonded; carbon atoms are classified by their hybridization state
and the chemical nature of their neighboring atoms. In other words, the aromaticity
associated with the C atom as part of the aromatic ring is favorable for NCC
blocking activity. Thus, the positive slope of the Atype_C_24 descriptor in
QSAR model revealed that NCC blocking activity increases with an increase in
hydrophobicity associated with this carbon. (c) Another thermodynamic descriptor
S_sssN also appeared in NCC QSAR model, and is defined as the summation of the
electrotopological indices for all the N atoms present in a compound that is
connected by three single bonds except hydrogen. Zhihua et al. [
74
] showed that
for peptide analogues electrotopological descriptors have both excellent structural
selectivity and activity estimation. The numerical values of electrotopological
descriptors computed for each atom in a compound encode information about
both the topological environment of that atom and electronic interactions due to
all other atoms in the compound. The topological relationship is based on the graph
distance to each atom. The electronic aspect is based on the intrinsic state and
perturbation due to the intrinsic state differences between atoms in the compound
[
74
,
75
]. The developed NCC QSAR model revealed a positive correlation with the
descriptor S_sssN, suggesting that the nature of the electronic environment in this
compound is necessary for potent NCC blocking activity.
The other two descriptors ADME_Solubility and Atype_N_68 selected by QSAR
model exhibited a negative correlation with the NCC blocking activity, as discussed in
detail below. (d) ADME_Solubility belongs to the ADME set of descriptors, and
is defined as the base 10 logarithm of the molar solubility of each compound in water,
predicted by linear regression methodology [
81
]. The presence of this descriptor
in QSAR model was correlated with a negative contribution toward NCC blocking
activity. (e) Atype_N_68 descriptor is of atom-type and is defined as N present in
an Al
3
N context in the compound. Al represents aliphatic groups and the
N atom linked with the three aliphatic groups in the compound (tertiary nature). The
negative slope of this descriptor in QSAR model revealed that NCC blocking activity
decreases with an increase in hydrophobicity associated with this nitrogen [
71
].
