title: Multivariate QSAR study on the antimutagenic activity of flavonoids against 3-NFA on Salmonella typhimurium TA98.
abstract: 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.
authors.affiliation: Curso de Farmácia, Centro de Ciências Médicas e Farmacêuticas, Universidade Estadual do Oeste do Paraná - Unioeste, Cascavel, PR, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Borges de Melo
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Ataide Martins
authors.forename: Teresa Cristina
authors.initials: TC
authors.lastname: Marinho Jorge
authors.forename: Marcelo Couto
authors.initials: MC
authors.lastname: Friozi
authors.forename: Márcia Miguel
authors.initials: MM
authors.lastname: Castro Ferreira
mesh_terms: D000465:Algorithms; D016587:Antimutagenic Agents / Q000737:chemistry* / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D005449:Fluorenes / Q000009:adverse effects* / Q000378:metabolism; D016018:Least-Squares Analysis; D008954:Models, Biological; D008958:Models, Molecular; D009153:Mutagens / Q000009:adverse effects* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
chemical_list: D016587:Antimutagenic Agents; D005419:Flavonoids; D005449:Fluorenes; D009153:Mutagens; C033643:3-nitrofluoranthene