Abstract.
A quantitative structureeactivity relationship
(QSAR) study of twenty flavonoid derivatives with antimutagenic
activity against 3-nitrofluoranthene (3-NFA) was performed by Partial
Least Squares (PLS), using Ordered Predictors Selection (OPS) algorithm
for variable selection. Four descriptors (PJI2, Mor27m, G1e and R4u+)
were selected and a good model (n
= 19; R2 = 0.747;
SEC = 0.332; PRESScal = 1.768; F(2,27) = 23.585; Q2LOO =
0.590; SEV = 0.388; PRESSval = 2.858; R2pred =
0.591; SEP = 0.394; AREpred = 5.230%; k
= 1.005; k' = 0.990; |R20 - R'20|
= 0.109) was built with two latent variables describing 83.410% of the
original information. Leave-N-out
cross validation (LNO) and y-randomization
were performed in order to confirm the robustness of the model. The
topological descriptors selected indicate that the antimutagenic
activity against 3-NFA depends on molecular size, shape and Sanderson
electronegativity of flavonoids. The proposed model may provide a
better understanding of the antimutagenic activity of flavonoids and
can be used as a guidance for proposition of new chemopreventive agents.
Keywords.
QSAR; Model Validation; Flavonoids; PLS; OPS.
Keywords Plus.