Synthesis and screening of an oroidin library against Pseudomonas aeruginosa biofilms.
A 50-compound library based on the marine natural product oroidin was synthesized and assayed for anti-biofilm activity against PAO1 and PA14, two strains of the medically relevant gamma-proteobacterium Pseudomonas aeruginosa. Through structure-activity relationship (SAR) analysis of analogues based on the oroidin template, several conclusions can be drawn as to what structural properties of the synthetic derivatives are necessary to elicit a biological response. Notably, the most active analogues identified were those that contained a 2-aminoimidazole (2-AI) motif and a dibrominated pyrrolecarboxamide subunit. Here we disclose the synthesis and subsequently determined biological activity of this unique class of compounds as inhibitors of biofilm formation that have no direct antibiotic effect.
Richards
Justin J
JJ
Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.
Ballard
T Eric
TE
Huigens
Robert W
RW
Melander
Christian
C
D018441:Biofilms; D003432:Cross-Linking Reagents / Q000737:chemistry; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D003432:Cross-Linking Reagents; D011758:Pyrroles; C077209:oroidin