Designing antibacterial compounds through a topological substructural approach.

A novel application of TOPological Substructural MOlecular DEsign (TOPS-MODE) was carried out in antibacterial drugs using computer-aided molecular design. Two series of compounds, one containing antibacterial and the other containing non-antibacterial compounds, were processed by a k-means cluster analysis in order to design training and predicting series. All clusters had a p-level < 0.005. Afterward, a linear classification function has been derived toward discrimination between antibacterial and non-antibacterial compounds. The model correctly classifies 94% of active and 86% of inactive compounds in the training series. More specifically, the model showed a global good classification of 91%, i.e., 263 cases out of 289. In predicting series, the model has shown overall predictabilities of 91 and 83% for active and inactive compounds, respectively. Thereby, the model has a global percentage of good classification of 89%. The TOPS-MODE approach, also, similarly compares with respect to one of the most useful models for antimicrobials selection reported to date.