Cheminformatics analysis of molecular datasets of transcription factors associated with quorum sensing in Pseudomonas aeruginosa

Transcription factors associated with quorum sensing in P. aeruginosa are promising targets for developing new adjuvants against infection by this pathogen. Regulation of these transcription factors offers the possibility of controlling multiple virulence factors related to them, as the development of biofilm, proteases, hydrogen cyanide, and others. Numerous molecules have been tested against those targets, but the keys responsible for antagonistic activity against these targets are unknown. In this work, we analyze the structure-activity relationships of active molecules tested against LasR, PqsR, and RhlR transcription factors to establish the structural characteristics associated. The compounds were classified as agonist, antagonist, and inactive. As part of the analysis, we conducted molecular complexity, scaffold analyses, activity cliffs analyses, and chemical space visualization to find characteristics associated with the biological activity. Several structural features were identified as important to antagonist activity in this study, highlighting molecular size and hydrogen bond acceptors.