Design, synthesis and activity against Staphylococcus epidermidis of 5-chloro-2- or 5-chloro-4-methyl-9H-xanthen-9-one and some of its derivatives.

Abstract

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 0.8µg/ml against ATCC 12228 strain, compared to linezolid (0.8µg/ml), ciprofloxacin (0.2µg/ml) or trimethoprim and sulfamethoxazole (0.8µg/ml). For the most active compound 3, genotoxicity assay with use of Salmonella enterica serovar Typhimurium revealed safety in terms of genotoxicity at concentration 75µg/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.