Ten new xanthone derivatives have been designed and synthesized for their potential antibacterial activity. All compounds have been screened against Staphylococcus epidermidis strains ATCC 12228 and clinical K/12/8915. The highest antibacterial activity was observed for compound 3: 5‐chloro‐2‐((4‐(2‐hydroxyethyl)piperazin‐1‐yl)methyl)‐9H‐xanthen‐9‐one dihydrochloride, exhibiting MIC of 0.8 µg/ml against ATCC 12228 strain, compared to linezolid (0.8 µg/ml), ciprofloxacin (0.2 µg/ml) or trimethoprim and sulfamethoxazole (0.8 µg/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75 µg/ml and antibacterial activity against Salmonella at all higher concentrations. A final in silico prediction of skin metabolism of compound 3 seems promising, indicating stability of the xanthone moiety in the metabolism process.
