Antibacterial and antibiofilm potential of De-O-methylsimmondsin from Cyanocohniella cycadae isolated from Cycas circinalis

The escalating threat of antimicrobial resistance necessitates the discovery of novel bioactive compounds from unexplored sources. This study reports, for the first time, the antibacterial and antibiofilm activity of De- O -methylsimmondsin isolated from Cyanocohniella cycadae , a cyanobacterium from the coralloid root of Cycas circinalis . The methanol extract demonstrated significant antibacterial activity against five pathogenic bacteria, with Pseudomonas aeruginosa (PA) showing the highest susceptibility (ZOI: 41.33 mm, MIC: 16 μg/mL). Notably, PA also exhibited maximum biofilm inhibition of 75.5% at 1 mg/mL concentration. HR-LC-MS analysis identified De- O -methylsimmondsin as the predominant bioactive compound. Molecular docking studies revealed high binding affinity of De- O -methylsimmondsin with PA virulence factors GDP-mannose dehydrogenase (−6.3 kcal/mol) and LasA protease (−6.7 kcal/mol), suggesting potential antibiofilm mechanisms. These findings highlight the therapeutic potential of cyanobacterial metabolites from symbiotic associations and warrant further investigation for antimicrobial drug development.