Quinazoline Derivatives of Imino-1,2,3-dithiazoles as Pseudomonas aeruginosa Biofilm Dispersal Agents

Biofilms represent a major clinical challenge, as bacteria embedded within these structures are highly tolerant of antibiotics. Among biofilm-forming pathogens, Pseudomonas aeruginosa is particularly problematic, as it forms persistent biofilms that cause acute and chronic infections, especially in immunocompromised patients.(1) Since chronic infections associated with biofilms require extensive treatment, they increase the risk of antimicrobial resistance.(2) In this context, novel therapeutic strategies are emerging, aiming to promote biofilm dispersion and thereby restore bacterial susceptibility to antimicrobial agents.

 In this study, a library of thirty-six N-arylimino-1,2,3-dithiazole derivatives was investigated for their capacity to promote the dispersion of P. aeruginosa biofilms using a crystal violet-based assay.(3) The most active candidates were further evaluated to determine their impact on bacterial growth, virulence, and cytotoxicity toward human cell lines. In addition, fluorescence anisotropy experiments were performed to explore potential effects on bacterial membrane properties and provide preliminary mechanistic insights.

 This study reveals that quinazoline-containing imino-1,2,3-dithiazoles exhibit biofilm-dispersing activity at micromolar concentrations. Importantly, these molecules do not impact bacterial growth dynamics of P. aeruginosa, do not enhance virulence, and exhibit no detectable cytotoxicity toward eukaryotic cells.

(1) Letizia, M.; Diggle, S. P.; Whiteley, M. Pseudomonas Aeruginosa: Ecology, Evolution, Pathogenesis and Antimicrobial Susceptibility. Nat. Rev. Microbiol. 2025, 23, 701–717. https://doi.org/10.1038/s41579-025-01193-8.

(2) Choi, V.; Rohn, J. L.; Stoodley, P.; Carugo, D.; Stride, E. Drug Delivery Strategies for Antibiofilm Therapy. Nat. Rev. Microbiol. 2023, 21, 555–572. https://doi.org/10.1038/s41579-023-00905-2.

(3) Gonzalez, M.; Tareau, A.-S.; de Crozals, D.; Layec, C.; Broudic, N.; Barreau, M.; Forge, A.; Lesouhaitier, O.; Fruit, C.; Chevalier, S.; Besson, T.; Tahrioui, A. Quinazoline-Derivatives of Imino-1,2,3-Dithiazoles Promote Biofilm Dispersion of Pseudomonas Aeruginosa. Pharmaceuticals 2025, 18, 1733. https://doi.org/10.3390/ph18111733.