Screening of antibacterial compounds with novel structure from the FDA approved drugs using machine learning methods.

Bacterial infection is one of the most important factors affecting the human life span. Elderly people are more harmed by bacterial infections due to their deficits in immunity. Because of the lack of new antibiotics in recent years, bacterial resistance has increasingly become a serious problem globally. In this study, an antibacterial compound predictor was constructed using the support vector machines and random forest methods and the data of the active and inactive antibacterial compounds from the ChEMBL database. The results showed that both models have excellent prediction performance (mean accuracy >0.9 and mean AUC >0.9 for the two models). We used the predictor to screen potential antibacterial compounds from FDA-approved drugs in the DrugBank database. The screening results showed that 1087 small-molecule drugs have potential antibacterial activity and 154 of them are FDA-approved antibacterial drugs, which accounts for 76.2% of the approved antibacterial drugs collected in this study. Through molecular fingerprint similarity analysis and common substructure analysis, we screened 8 predicted antibacterial small-molecule compounds with novel structures compared with known antibacterial drugs, and 5 of them are widely used in the treatment of various tumors. This study provides a new insight for predicting antibacterial compounds by using approved drugs, the predicted compounds might be used to treat bacterial infections and extend lifespan.