Development of xanthone derivatives as effective broad-spectrum antimicrobials: Disrupting cell wall and inhibiting DNA synthesis

Xanthones are intriguing sources of antimicrobials, despite a scarcity of extensive investigations into their mechanisms of action. Here, we reported the development of a series of xanthone derivatives, among which compound XT17 displayed strong broad-spectrum antibacterial activity, weak hemolytic activity and low cytotoxicity against mammalian cell lines, low frequencies of drug resistance, and potent in vivo efficacy in Staphylococcu aureus or Pseudomonas aeruginosa induced murine corneal infection models.

Compound XT17 presented a multifaceted mode of actions, involving the disruption of cell wall by interacting with lipoteichoic acid or lipopolysaccharides and the suppression of DNA synthesis. A further docking study confirmed the capability of compound XT17 to form a stable complex with the bacterial gyrase enzyme. This work could offer an innovative design strategy for developing broad-spectrum therapeutic agents against drug-resistant bacteria.