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

作者：de Melo Eduardo Borges; Ataide Martins Joao Paulo; Marinho Jorge Teresa Cristina; Friozi Marcelo Couto; Castro Ferreira Marcia Miguel

来源：European Journal of Medicinal Chemistry, 2010, 45(10): 4562-4569.

DOI：10.1016/j.ejmech.2010.07.017

• QSAR
• Model validation
• Flavonoids
• PLS
• OPS

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 divided by) were selected and a good model (n = 19; R(2) = 0.747; SEC = 0.332, PRESS(cal) = 1.768, F((2.27)) = 23.585; Q(LOO)(2) = 0.590; SEV = 0.388; PRESS(val) = 2 858; R(pred)(2) = 0.591; SEP = 0.394; ARE(pred) = 5.230%, k = 1.005; k' = 0.990; vertical bar R(0)(2) -R(0)'(2)vertical bar = 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.

• 出版日期2010-10