Engineering the novel azobenzene‐based molecular photoswitches for suppressing bacterial infection through dynamic regulation of biofilm formation

Abstract BACKGROUND Bacterial biofilm is a strong fortress for bacteria to resist harsh external environments, which can enhance their tolerance and exacerbate the drug/pesticide resistance risk. Currently, photopharmacology provides an advanced approach via precise spatiotemporal control for regulating biological activities by light‐controlling the molecular configurations, thereby having enormous potential in the development of drug/pesticides. RESULTS To further expand the photopharmacology application for discovering new antibiofilm agents, we prepared a series of light‐controlled azo‐active molecules and explored their photo isomerization, fatigue resistance, and anti‐biofilm performance. Furthermore, their mechanisms of inhibiting biofilm formation were systematically investigated. Overall, designed azo‐derivative A11 featured excellent anti‐ Xoo activity with an half‐maximal effective concentration (EC 50 ) value of 5.45 μg mL −1 , and the EC 50 value could be further elevated to 2.19 μg mL −1 after ultraviolet irradiation (converted as cis ‐configuration). The photo‐switching behavior showed that A11 had outstanding anti‐fatigue properties. An in‐depth analysis of the action mechanism showed that A11 could effectively inhibit biofilm formation and the expression of relevant virulence factors. This performance could be dynamically regulated via loading with private light‐switch property. CONCLUSION In this work, designed light‐controlled azo molecules provide a new model for resisting bacterial infection via dynamic regulation of bacterial biofilm formation. © 2024 Society of Chemical Industry.