Abstract.
The molecular orbital method PM3 is employed to calculate a set of
molecular descriptors (variables) for 36 deoxy analogs of
1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) with anti-HIV-l
activity. Pattern recognition methods, principal
component analysis (PCA) and stepwise discriminant analysis (SDA) were
employed in order to reduce dimensionality and
investigate which subset of variables should be more effective for
classifying the HEPT-analog compounds according to their degree
of anti-HIV-l activity. The PCA showed that the variables log P
(partition coefficient), MR (molecular refractivity), DHf
(heat
of
formation), QN (net atomic charge
on atoms 2 and 3), and c (Mulliken's electronegativity)
are responsible for the separation
between compounds with higher and lower anti-HIV-1 activity. By using
the SDA we have found the following descriptors as
responsible for the separation between the active and less active compounds:
log P (partition coefficient), c (Mulliken's
electronegativity), m (dipole moment), Q4
(net atomic charge on atom 4), and t2
(torsional angle). From the SDA we present a
prediction rule for classifying new HEPT-analog compounds with anti-HIV-l
activity.
Keywords.
Structure-Activity Relationship; PM3; Principal Component Analysis;
Stepwise Discriminant Analysis.
Keywords Plus.
QSAR; Inhibitors; Descriptors; Derivatives; Flavanoids; Charges.