Structure-activity relationships of phenyl-furanyl-rhodanines as inhibitors of RNA polymerase with antibacterial activity on biofilms.
The dramatic rise of antibiotic-resistant bacteria over the past two decades has stressed the need for completely novel classes of antibacterial agents. Accordingly, recent advances in the study of prokaryotic transcription open new opportunities for such molecules. This paper reports the structure-activity relationships of a series of phenyl-furanyl-rhodanines (PFRs) as antibacterial inhibitors of RNA polymerase (RNAP). The molecules have been evaluated for their ability to inhibit transcription and affect growth of bacteria living in suspension or in a biofilm and for their propensity to interact with serum albumin, a critical parameter for antibacterial drug discovery. The most active of these molecules inhibit Escherichia coli RNAP transcription at concentrations of </=10 microM and have promising activities against various Gram-positive pathogens including Staphylococcus epidermidis biofilms, a major cause of nosocomial infection.
Villain-Guillot
Philippe
P
CNRS UMR 5236, Centre d'études d'agents Pathogènes et Biotechnologie pour la Santé, and CNRS UMR 5247, Institut des Biomolécules Max Mousseron, Faculté de Pharmacie, 15 avenue Flahault, 34093 Montpellier cedex 5, France.
Gualtieri
Maxime
M
Bastide
Lionel
L
Roquet
Françoise
F
Martinez
Jean
J
Amblard
Muriel
M
Pugniere
Martine
M
Leonetti
Jean-Paul
JP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018441:Biofilms; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D008826:Microbial Sensitivity Tests; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D005663:Furans; D012236:Rhodanine; D012321:DNA-Directed RNA Polymerases