Medicinal Chemistry

QSAR Models for Prediction of Binding and Inhibitory Properties of [(E)-2- R-vinyl]benzene Derivatives with Therapeutic Effects against Helicobacter pylori

Abstract

Juan J Galano and Javier Sancho

Helicobacter pylori is a gram-negative bacterium that infects the luminal surface of the human gastric epithelium. Around one half of the world’s population is thought to be infected by this bacterium, which is able to develop diseases such as peptic ulcer or gastric cancer. Eradication of Helicobacter pylori is becoming increasingly difficult due to resistance to common antibiotics. In previous work we have shown that an essential protein, flavodoxin, constitutes a target for the development of novel, specific antibiotics against infection caused by this microorganism, and we have described compounds sharing the [(E)-2-R-vinyl]benzene scaffold that exhibit bactericidal properties against Helicobacter pylori cultures. Based on the affinity and activity of 24 such compounds we have now developed QSAR models for affinity and minimal inhibitory concentration that will guide the improvement of antibacterial compounds based in the [(E)-2-R-vinyl]benzene scaffold. The two models show high statistical correlation and predictive capacity. Discovering novel chemicals with specific antimicrobial properties against Helicobacter pylori , and presumably not affected by existing resistances, will be of great help for the treatment of the diseases associated with this bacteriu