Pulvinones as bacterial cell wall biosynthesis inhibitors.
Pulvinones were synthesized (>180) in arrays and evaluated as inhibitors of early stage cell wall biosynthesis enzymes MurA-MurD. Several pulvinones inhibited Mur enzymes with IC(50)'s in the 1-10 microg/mL range and demonstrated antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphyloccus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae.
Antane
Schuyler
S
Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, Princeton, NJ 08543, USA. antanes@wyeth.com
Caufield
Craig E
CE
Hu
William
W
Keeney
David
D
Labthavikul
Pornpen
P
Morris
Koi
K
Naughton
Shaughnessy M
SM
Petersen
Peter J
PJ
Rasmussen
Beth A
BA
Singh
Guy
G
Yang
Youjun
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000138:chemical synthesis*; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D010406:Penicillins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002264:Carboxylic Acids; D007783:Lactones; D010406:Penicillins; D014640:Vancomycin; C492654:pulvinic acid; D008712:Methicillin