RATIONALLY DESIGNED LAWSONE DERIVATIVES AS ANTIMICROBIALS AGAINST MULTIDRUG-RESISTANT STAPHYLOCOCCUS AUREUS

摘要

Naphthoquinone derivatives of Lawsone have been found to be effective against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Such compounds generally contain a substituent group at the 3-position of a specific naphthoquinone compound, i.e. 2-hydroxy-1,4-naphthoquinone. One of these derivatives referred to as compound 6c in the series exhibits potent antimicrobial activity that is comparable to that of the two commercial antibiotics ofloxacin and ciprofloxacin against the two strains of methicillin sensitive Staphylococcus aureus (MSSA; ATCC 29213 and ATCC 6538). In the case of two strains of MRSA (ATCC BAA-44 and ATCC BAA-1717) that have developed drug resistance to both ofloxacin and ciprofloxacin, the antimicrobial activity of 6c can almost rival that of vancomycin and daptomycin. Furthermore, 6c is also effective against vancomycin-intermediate and daptomycin non-susceptible strain of MRSA (ATCC 700699). Besides the efficacy, 6c has a much improved drug resistance profile in comparison with the conventional antibiotics.