Transition metal diamine complexes with antimicrobial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA)

摘要

Pentaalkylcyclopentadienyl (Cp*(R)) iridium (Ir) and cobalt (Co) 1,2-diamine complexes were synthesized. Susceptibility of Staphylococcus aureus and recent patient methicillin-resistant S. aureus (MRSA) isolates to the transition metal-diamine complexes were measured by broth microdilution and reported as the MIC and MBC. Hemolytic activities of the transition metal-complexes as well as toxicity toward Vero cells were also measured. The transition metal complex of Cp*Ir-R with cis-1,2-diaminocyclohexane, had strong antibiotic activity against S. aureus and MRSA (MIC = 4 mu g mL(-1), MBC = 8 mu g mL(-1)) strains and killed 99% of S. aureus cells in 6 hours. Stronger antibiotic activity was associated with the presence of octyl linked to the cyclopentadienyl group and cyclohexane as the diamine backbone. Activity was greatly diminished by trior tetramethylation of the nitrogen of the diamine. A cyclopentadienylcobalt complex of cis-1,2-diaminocyclohexane also showed significant anti-microbial activity against both S. aureus and MRSA strains. The absence of hemolytic activity, Vero cell cytotoxicity and the significant anti-microbial activity of several members of the family of compounds reported suggest this is an area worth further development.