Curso de Farmácia, Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná - Unioeste, Cascavel, PR, Brazil.
Eur J Med Chem. 2010 Oct;45(10):4562-9. doi: 10.1016/j.ejmech.2010.07.017. Epub 2010 Jul 17.
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; 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; |R(02) - 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.
采用偏最小二乘法（PLS），并结合有序预测器选择（OPS）算法进行变量选择，对具有抗 3-硝基芴（3-NFA）致突变活性的 20 种黄酮类衍生物进行定量构效关系（QSAR）研究。选择了四个描述符（PJI2、Mor27m、G1e 和 R4u+），建立了一个良好的模型（n = 19；R² = 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；|R（02）-R'（02）|= 0.109），该模型用两个描述符描述了 83.410%的原始信息。采用留一法交叉验证（LNO）和 y-随机化进行验证，以确认模型的稳健性。所选拓扑描述符表明，黄酮类化合物对 3-NFA 的抗突变活性取决于分子大小、形状和桑德森电负性。所提出的模型可以更好地理解黄酮类化合物的抗突变活性，并可用于提出新的化学预防剂。
