Acid-Induced Epimerization of Eudesmin to Epieudesmin: Rapid Bactericidal and Antibiofilm Activity Against Helicobacter pylori.

Helicobacter pylori infection is associated with severe gastroduodenal pathologies. This study evaluated the bactericidal and antibiofilm activities of eudesmin, a furanofuran lignan from Araucaria araucana, and its acid-induced epimer, epieudesmin, against clinical isolates and the H. pylori ATCC 43504 strain. Virulence profiles and antibiotic susceptibility (CLSI/EUCAST) were determined. Antibacterial effects were assessed via minimum inhibitory concentration (MIC), checkerboard assays, time-kill kinetics, and urease activity. Biofilm reduction and morphological alterations were analyzed using crystal violet staining and scanning electron microscopy, respectively. Cytotoxicity was evaluated in HepG2 cells. Clinical strains exhibited distinct virulence and multidrug-resistance patterns. Both lignans displayed rapid antibacterial activity (MIC: 0.78-3.12 µg/mL) without antagonistic interactions with co-administered antibiotics and significantly reduced biofilm biomass (p < 0.0001). Eudesmin and epieudesmin effectively inhibit H. pylori growth and biofilm formation, while sublethal concentrations disrupted biofilm integrity and induced a bacillary-to-coccoid transition. Toxicity of both compounds was evaluated in HepG2 cells till 50 µg/mL showing a similar pattern, reducing cell viability up to 30% at almost 25 µg/mL, highlighting its potential as a non-antibiotic complementary therapeutic agent, although further in vivo and clinical studies are warranted to confirm its therapeutic applicability.