Antibacterial activity of substituted dibenzo[a,g]quinolizin-7-ium derivatives.
Berberine is a substituted dibenzo[a,g]quinolizin-7-ium derivative whose modest antibiotic activity is derived from its disruptive impact on the function of the essential bacterial cell division protein FtsZ. The present study reveals that the presence of a biphenyl substituent at either the 2- or 12-position of structurally-related dibenzo[a,g]quinolizin-7-ium derivatives significantly enhances antibacterial potency versus Staphylococcus aureus and Enterococcus faecalis. Studies with purified S. aureus FtsZ demonstrate that both 2- and 12-biphenyl dibenzo[a,g]quinolizin-7-ium derivatives act as enhancers of FtsZ self-polymerization.
TAXIS Pharmaceuticals Inc., North Brunswick, NJ 08092, USA.
Ajit
A
Parhi
Songfeng
S
Lu
Cody
C
Kelley
Malvika
M
Kaul
Daniel S
DS
Pilch
Edmond J
EJ
LaVoie
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001599:Berberine / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013293:Enterococcus faecalis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011807:Quinolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D011807:Quinolizines; D001599:Berberine