title: Molecular docking study to evaluate the carcinogenic potential and mammalian toxicity of thiophosphonate pesticides by cluster and discriminant analysis.
abstract: In this paper, the carcinogenic potential and mammalian toxicity on rodents, based on the quantitative relationship models between structure and biological activity (QSAR), were evaluated. The carcinogenicity and acute toxicity were evaluated by docking molecular physicochemical descriptors, on a series of 33 thiophosphonates. These properties, mainly hydrophobicity, electronic distribution, hydrogen bonding characteristics, molecule size and flexibility, and the presence of various pharmacophoric features, influence the behavior of molecule in a living organism, including bioavailability, transport properties, affinity to proteins, reactivity, toxicity, metabolic stability and many others. The model was validated using linear regression methods: principal component analysis (PCA), partial least squares (PLS) and multiple linear regression (MLR); non-linear regression methods: cluster analysis (CA) and discriminant analysis (DA); and neural network analysis: probabilistic neural network (PNN), identifying the best predictor.
authors.affiliation: West University of Timisoara, Faculty of Chemistry, Biology, Geography, Dept. of Biology-Chemistry, 16 Pestalozzi Street, 300115 Timisoara, Romania.
authors.forename: Alina-Maria
authors.initials: AM
authors.lastname: Petrescu
authors.affiliation: West University of Timisoara, Faculty of Chemistry, Biology, Geography, Dept. of Biology-Chemistry, 16 Pestalozzi Street, 300115 Timisoara, Romania; Institute of Chemistry Timisoara of Romanian Academy, 24 Mihai Viteazu Bvd., 300223 Timisoara, Romania. Electronic address: ilia@acad-icht.tm.edu.ro.
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Ilia
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D016000:Cluster Analysis; D016002:Discriminant Analysis; D008322:Mammals; D062105:Molecular Docking Simulation; D063085:Organothiophosphonates / Q000737:chemistry / Q000633:toxicity*; D047493:PPAR alpha; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012377:Rodentia
chemical_list: D002273:Carcinogens; D063085:Organothiophosphonates; D047493:PPAR alpha; D010575:Pesticides
keywords: Carcinogenicity; Cluster analysis; Discriminant analysis; Probabilistic neural network; QSAR; Thiophosphonates