Benzoxazine series of histidine kinase inhibitors as potential antimicrobial agents with activity against enterococci.
BACKGROUND
Antibacterial activity of three members of a benzoxazine series of histidine kinase inhibitors ( 4a , 4b and 6 ) was studied on standard strains, and with 4b also on clinical isolates of enterococci.


METHODS
Susceptibility to each compound was tested using a broth macrodilution method with a range of dilutions from 0.016 to 128 microg/ml on four standard strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212) and in the case of 4b also on 52 clinical isolates of enterococci (7 vancomycin-susceptible E. faecalis, 15 vancomycin-susceptible Enterococcus faecium and 30 vancomycin-resistant E. faecium), and on two additional standard strains (S. aureus ATCC 43300 and E. faecalis ATCC 51299).


RESULTS
Neither of the compounds inhibited the growth of E. coli ATCC 25922 or P. aeruginosa ATCC 27853. Compound 4b inhibited the growth of S. aureus ATCC 29213 at 8 microg/ml, S. aureus ATCC 43300 at 32 microg/ml, E. faecalis ATCC 29212, and E. faecalis ATCC 51299 at 16 microg/ml, while 4a and 6 did so at higher concentrations. For clinical isolates of enterococci, the minimal inhibitory concentrations of 4b were in the range of 0.5-16 microg/ml.


CONCLUSIONS
Compound 4b promises to be a potentially useful antimicrobial agent for vancomycin-susceptible and -resistant enterococci.
Mueller-Premru
Manica
M
Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia. manica.mueller-premru@mf.uni-lj.si
Zidar
Nace
N
Spik
Vesna Cvitković
VC
Krope
Adrijana
A
Kikelj
Danijel
D
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D048588:Benzoxazines / Q000494:pharmacology*; D016983:Enterococcus / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D000071677:Histidine Kinase; D008826:Microbial Sensitivity Tests; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D048588:Benzoxazines; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D000071677:Histidine Kinase