A topological substructural approach applied to the computational prediction of rodent carcinogenicity.
Bioorg Med Chem
; 13(7): 2477-88, 2005 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-15755650
The carcinogenic activity has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A discriminant model was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 189 compounds. The percentage of correct classification was 76.32%. The predictive power of the model was validated by three test: an external test set (compounds not used in the develop of the model, with a 72.97% of good classification), a leave-group-out cross-validation procedure (4-fold full cross-validation, removing 20% of compounds in each cycle, with a good prediction of 76.31%) and two external prediction sets (the first and second exercises of the National Toxicology Program). This methodology evidenced that the hydrophobicity increase the carcinogenic activity and the dipole moment of the molecule decrease it; suggesting the capacity of the TOPS-MODE descriptors to estimate this property for new drug candidates. Finally, the positive and negative fragment contributions to the carcinogenic activity were identified (structural alerts) and their potentialities in the lead generation process and in the design of 'safer' chemicals were evaluated.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
/
Carcinógenos
/
Testes de Carcinogenicidade
/
Relação Quantitativa Estrutura-Atividade
/
Modelos Teóricos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Cuba
País de publicação:
Reino Unido