Abstract:
: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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Helguera AM,Cabrera Pérez MA,González MP,Ruiz RM,González Díaz Hdoi
10.1016/j.bmc.2005.01.035subject
Has Abstractpub_date
2005-04-01 00:00:00pages
2477-88issue
7eissn
0968-0896issn
1464-3391pii
S0968-0896(05)00059-3journal_volume
13pub_type
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