Two novel synthetic xanthenodiones as antimicrobial, anti-adhesive and antibiofilm compounds against methicillin resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is widely recognized as a causative agent for various infections acquired in healthcare settings as well as in the community. Given the limited availability of effective antimicrobial agents to combat MRSA infections, there is an increasing need to explore alternative therapeutic strategies. This study aimed to assess the antimicrobial, anti-adhesive, anti-biofilm properties, and toxicity of 175 newly synthesized compounds, belonging to seven different classes, against MRSA. Initially, the compounds underwent screening for antimicrobial activity using the agar diffusion method. Subsequently, active compounds underwent further evaluation to determine their minimum inhibitory concentrations through microdilution. Anti-biofilm and anti-adhesive properties were assessed using the crystal violet method, while toxicity was tested using the alternative infection model Galleria mellonella. Among the tested compounds, two xanthenodiones exhibited the most promising activities, displaying bactericidal effects along with anti-adhesive and anti-biofilm properties. Moreover, the observed non-toxicity in G. mellonella larvae suggests that these compounds hold significant potential as alternative therapeutic options to address the escalating challenge of MRSA resistance in both hospital and community settings.