In vitro properties of antimicrobial bromotyrosine alkaloids.
A bromotyrosine alkaloid family of antimicrobial agents was synthesized using the known structure of a natural inhibitor of the mycobacterial mycothiol S-conjugate amidase (MCA) as a template. This series of compounds represents a novel class of anti-infective agents against Gram-positive pathogens, including mycobacteria and meticillin- and vancomycin-resistant Staphylococcus aureus. The fact that these compounds are active against mycobacterial strains in which the MCA gene is deleted and against Gram-positive bacteria lacking mycothiol suggests the existence of an alternative target for these compounds. One member of this family, EXEG1706, was identified as the lead compound possessing low MICs (2.5-25 microg ml(-1)) for several clinical isolates, whilst having low toxicity for THP-1 monocytes and macrophages.
Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada.
Neora
N
Pick
Department of Biology, California State University - Fresno, Fresno, CA 937401, USA.|Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada.
Mamta
M
Rawat
Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada.
Dorit
D
Arad
Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA.
Jiong
J
Lan
Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA.
Junfa
J
Fan
Department of Chemistry, University of Rochester, Rochester, NY 14627-0216, USA.
Andrew S
AS
Kende
Division of Infectious Diseases, University of British Columbia, Vancouver, BC V5Z 3J5, Canada.
Yossef
Y
Av-Gay
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002460:Cell Line; D005463:Fluoroacetates; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008956:Models, Chemical; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000470:Alkaloids; D000900:Anti-Bacterial Agents; C509892:EXEG1706; D005463:Fluoroacetates; C475724:bromotyrosine; D014443:Tyrosine