Tiratricol neutralizes bacterial endotoxins and reduces lipopolysaccharide-induced TNF-alpha production in the cell.
The screening of a commercially available library of compounds has proved a successful strategy for the identification of a lead compound in a drug discovery programme. Here, we analysed 880 off-patent drugs, which initially comprised the Prestwick Chemical library, as sources of bacterial endotoxin neutralizers. We identified 3,3',5-triiodo-thyroacetic acid (tiratricol) as a non-antibacterial compound that neutralizes the toxic lipopolysaccharide.
Cascales
Laura
L
Department of Medicinal Chemistry, Centro de Investigaciones Principe Felipe, E-46013 Valencia, Spain.
Mas-Moruno
Carlos
C
Tamborero
Silvia
S
Aceña
José Luis
JL
Sanz-Cervera
Juan F
JF
Fustero
Santos
S
Cruz
Luis J
LJ
Mora
Puig
P
Albericio
Fernando
F
Pérez-Payá
Enrique
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D013329:Structure-Activity Relationship; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid