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As the persistent resistance of  Staphylococcus aureus  to available antibiotics is associated with high infection incidence, mortality rate and treatment cost, novel antibacterial agents with innovative therapeutic targets must be developed. 3,3′-(4-Nitrobenzylidene)-bis-(4-hydroxycoumarin) (NBH), a dicoumarin derivative, was reported to exert antibacterial activity. This study investigated the underlying mechanisms of  in vivo  and  in vitro  activities of NBH against  S. aureus . NBH exerted bactericidal effects against the tested  S. aureus  and  Staphylococcus epidermidis  strains  in vitro , with low cytotoxicity and resistance and high plasma stability. NBH also exhibited therapeutic effects  in vivo  on septicaemic mice. Results of molecular docking and analysis on morphological change, DNA production and polymerase inhibition suggested that DNA polymerase could be the target of NBH. These findings indicated that dicoumarin derivatives, which interfere with DNA replication, could be developed as a potential agent against  S. aureus , particularly methicillin-resistant strains.

scientific reports

Selective in vivo and in vitro activities of 3,3′-4-nitrobenzylidene-bis-4-hydroxycoumarin against methicillin-resistant Staphylococcus aureus by inhibition of DNA polymerase III