Synthesis of 3-O-methylviridicatin analogues with improved anti-TNF-alpha properties.
We synthesized 3-O-methylviridicatin and several analogues of this fungal metabolite. We showed that replacement of the methoxy moiety by a thiomethyl enhanced dramatically its ability to inhibit TNF-alpha secretion. These results strongly suggest that 4-phenyl-3-methylthioquinolinone may provide the basis for the development of new anti-inflammatory agents.
Ribeiro
Nigel
N
UMR 7175 LC1, ULP-CNRS, Faculté de Pharmacie, 67401 Illkirch, France.
Tabaka
Helena
H
Peluso
Jean
J
Fetzer
Ludivine
L
Nebigil
Can
C
Dumont
Serge
S
Muller
Christian D
CD
Désaubry
Laurent
L
D002478:Cells, Cultured; D006801:Humans; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
C116810:3-O-methylviridicatin; D006912:Hydroxyquinolines; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha