Aliuska Helguera Morales

PubMed2006

A radial-distribution-function approach for predicting rodent carcinogenicity.

Carcinogenic activity has been investigated using the Radial-Distribution-Function (RDF) approach. A discriminant model was developed to predict the carcinogenic and non-carcinogenic activity on a data set of 188 compounds. The percentage of overall classification was 76.4% for the carcinogenic chemicals and 72.5% for the non-carcinogenic chemicals. The predictive power of the model was validated by two tests: a cross-validation by the resubstitution technique and a test set (compounds not used in the development of the model) with 79.3 and 72.5% good classification, respectively. The RDF descriptors were compared with eight other methodologies; Constitutional, Molecular walks counts, Galvez topological charge indices, 2D autocorrelations, Randić molecular profiles, Geometrical, 3D-MORSE, and WHIM, demonstrating that the RDF descriptors are better to the rest of the approaches used.

Animals↗

PubMed2006

Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity.

Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables.

Animals↗