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 discovering new adjuvants against infection with this pathogen. Regulation of these transcription factors offers the possibility of controlling multiple virulence factors related to them as biofilm development, proteases, hydrogen cyanide, among others. Numerous molecules have been tested against these targets, however, the keys responsible for antagonistic activity are still unknown. In this work, the structure–activity relationships of active molecules tested against LasR, PqsR, and RhlR transcription factors are analyzed in order to establish the structural characteristics associated. As part of the study, molecular complexity, scaffold, activity cliffs, and chemical space visualization analyses were conducted to find out characteristics associated with biological activity. In this study, several structural features were identified as significant for antagonist activity, highlighting molecular size and hydrogen bond acceptors.