Document Report Card

ID: ALA1142978

Journal: J Med Chem

Title: Probing the anticancer activity of nucleoside analogues: a QSAR model approach using an internally consistent training set.

Authors: Helguera AM, Rodríguez-Borges JE, García-Mera X, Fernández F, Cordeiro MN.

Abstract: The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsewhere, and tested in a single cytotoxic assay under the same experimental conditions, we recognized a unique opportunity to attempt to build predictive QSAR models. Here, we report a systematic evaluation of classification models to probe anticancer activity, based on linear discriminant analysis along with 2D-molecular descriptors. This strategy afforded a final QSAR model with very good overall accuracy and predictability on external data. Finally, we search for similarities between the natural nucleosides, present in RNA/DNA, and the active nucleosides well-predicted by the model. The structural information then gathered and the QSAR model per se shall aid in the future design of novel potent anticancer nucleosides.

CiteXplore: 17341060

DOI: 10.1021/jm061445m