Chemistry Reference
In-Depth Information
decrease in activity, giving evidence that the carboxamide group is important to the
hypocholesterolaemic activity of pine resin amides. Finally, the quantitative structure-
activity equation was obtained, in which σ is the Hammett electronic substituent
constant and E
s
(AMD) is a set of steric parameters for
ortho
substituents. These two
parameters are important factors which affect the hypocholesterolaemic activities of
N-phenyl-delta 8-dihydroabietamide analogues.
Scheme 6.22
Structure of
N
-phenyl-delta 8-dihydroabietamide analogues (
87
)
Linear discriminant analysis (LDA) is a statistical technique that aims to find the linear
combination of features which best separates two or more classes of objects or events.
The anticonvulsant activity of abietic acid has been discovered through application of
linear discriminant analysis [63]. LDA was performed to derive discriminant functions
based on two-dimensional descriptors and capable of distinguishing anticonvulsant
from nonanticonvulsant compounds. Through application in virtual screening of the
discriminant function which performed best in the validation steps, abietic acid (
1
)
was identified as a potential new anticonvulsant agent. The anticonvulsant activity
of abietic acid at 30 and 100 mg/kg was confirmed in the maximal electroshock
test, both orally and intraperitoneal. Abietic acid may be a candidate for structural
optimisation for the development of series of new anticonvulsant compounds. LDA
based on two-dimensional descriptors was confirmed as a powerful tool to be applied
in the effective discovery of new therapeutic agents.
However, the ultimate test of the QSAR model will be used to predict activities for
novel compounds with structures which are similar to those used in these studies.
Such results are of great benefit to research efforts to discover and synthesise active
compounds.
