The antimicrobial activities of 43 naturally occurring and synthetic coumarins were studied. Using a microtitre assay developed in-house, a range of Gram-positive and Gram-negative bacteria, including a hospital isolate of methicillin-resistant Staphylococcus aureus (MRSA), were utilised. The coumarins exhibiting good bioactivity (i.e. a lowminimum inhibitory concentration) against two S. aureus strains were then assessed for their antimicrobial activities against a range of eight clinically isolated MRSA strains. The study showed that nearly one-half of the tested compounds displayed antimicrobial activity. Sixteen of these coumarins also possessed resistance-modifying activity, which reversed the resistance mechanism in MRSA allowing the antimicrobial oxacillin to exert an enhanced effect against an MRSA hospital strain. When tested in combination with oxacillin, 8-iodo-5,7-dihydroxycoumarin (32) had a similar activity to vancomycin, which is the current drug of choice for the treatment of MRSA infections. (C) 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.