title: Probabilistic neural network multiple classifier system for predicting the genotoxicity of quinolone and quinoline derivatives.
abstract: Quinolone and quinoline are known to be liver carcinogens in rodents, and a number of their derivatives have been shown to exhibit mutagenicity in the Ames test, using Salmonella typhimurium strain TA 100 in the presence of S9. Both the carcinogenicity and the mutagenicity of quinolone and quinoline derivatives, as determined by SAS, can be attributed to their genotoxicity potential. This potential, which is measured by genotoxicity tests, is a good indication of carcinogenicity and mutagenicity because compounds that are positive in these tests have the potential to be human carcinogens and/or mutagens. In this study, a collection of quinolone and quinoline derivatives' carcinogenicity is determined by qualitatively predicting their genotoxicity potential with predictive PNN (probabilistic neural network) classification models. In addition, a multiple classifier system is also developed to improve the predictability of genotoxicity. Superior results are seen with the multiple classifier system over the individual PNN classification models. With the multiple classifier system, 89.4% of the quinolone derivatives were predicted correctly, and higher predictability is seen with the quinoline derivatives at 92.2% correct. The multiple classifier system not only is able to accurately predict the genotoxicity but also provides an insight about the main determinants of genotoxicity of the quinolone and quinoline derivatives. Thus, the PNN multiple classifier system generated in this study is a beneficial contributor toward predictive toxicology in the design of less carcinogenic bioactive compounds.
authors.affiliation: Department of Chemistry, Penn State University, University Park, Pennsylvania 16802, USA.
authors.forename: Linnan
authors.initials: L
authors.lastname: He
authors.forename: Peter C
authors.initials: PC
authors.lastname: Jurs
authors.forename: Constantine
authors.initials: C
authors.lastname: Kreatsoulas
authors.forename: Laura L
authors.initials: LL
authors.lastname: Custer
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Durham
authors.forename: Greg M
authors.initials: GM
authors.lastname: Pearl
mesh_terms: D000818:Animals; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000145:classification* / Q000633:toxicity*; D016571:Neural Networks, Computer; D015363:Quinolones / Q000737:chemistry / Q000145:classification* / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D009153:Mutagens; D015363:Quinolones