Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA efflux pump in Staphylococcus aureus.
The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as NorA efflux pump inhibitors indicated 5-nitro-2-(3-methoxycarbonyl)phenyl-1H-indole was a slightly more potent inhibitor than the lead INF55. A promising new antibacterial lead compound against S. aureus (2-phenyl-1H-indol-5-yl)-methanol, was also found.
Ambrus
Joseph I
JI
School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia.
Kelso
Michael J
MJ
Bremner
John B
JB
Ball
Anthony R
AR
Casadei
Gabriele
G
Lewis
Kim
K
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002939:Ciprofloxacin / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010165:Palladium / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D007211:Indoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010165:Palladium; D012238:Rhodium; C530574:INF55 compound; C075040:NorA protein, Staphylococcus