Pyrrolidinedione derivatives as antibacterial agents with a novel mode of action.
The pseudopeptide pyrrolidinedione natural products moiramide B and andrimid represent a new class of antibiotics that target bacterial fatty acid biosynthesis. Structure-activity relationship (SAR) studies revealed a high degree of variability for the fatty acid side chain, allowing optimization of physicochemical parameters, and a restricted SAR for the pyrrolidinedione group, indicating major relevance of this subunit for efficient target binding.
Pohlmann
Jens
J
Department of Medicinal Chemistry, Bayer HealthCare AG, D-42096 Wuppertal, Germany.
Lampe
Thomas
T
Shimada
Mitsuyuki
M
Nell
Peter G
PG
Pernerstorfer
Josef
J
Svenstrup
Niels
N
Brunner
Nina A
NA
Schiffer
Guido
G
Freiberg
Christoph
C
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors; D000577:Amides; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005227:Fatty Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D011090:Polyenes; D011758:Pyrroles; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis* / Q000494:pharmacology
D000577:Amides; D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D011090:Polyenes; D011758:Pyrroles; D013388:Succinimides; C487819:moiramide B; C088069:andrimid; D000103:Acetyl-CoA Carboxylase