From Drug Repurposing to Benzoxaborole Synthesis: Targeting LexA in Bacterial SOS Response

The rapid emergence of antimicrobial resistance (AMR) urgently demands innovative antibacterial strategies beyond conventional antibiotics. In this context, targeting essential bacterial pathways involved in stress response and survival represents a promising approach to counteract resistant strains. Among these, the bacterial SOS response plays a crucial role, as it promotes DNA repair, mutagenesis, filamentation, and biofilm formation. The transcriptional repressor LexA is the central regulator of this pathway and represents a promising target for novel antibacterial strategies. Importantly, its absence in eukaryotic cells makes it a highly selective target. In this study, we pursue the development of LexA inhibitors through a dual approach combining drug repurposing of FDA-approved benzoxaboroles with structure-based chemical optimization.