Multivariate QSAR study on the antimutagenic activity of flavonoids against 3-NFA on Salmonella typhimurium TA98

A quantitative structure–activity 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; QLOO2 = 0.590; SEV = 0.388; PRESSval = 2.858; Rpred2 = 0.591; SEP = 0.394; AREpred = 5.230%; k = 1.005; k  ′ = 0.990; |R02−R′02| = 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.

QSAR model for twenty antimutagenic flavonoids was built using four topological descriptors, fully validated and chemically interpreted. Biological activity depends on molecular size, shape and Sanderson electronegativity.Figure optionsDownload as PowerPoint slide