Inhibition of NF-kB and metalloproteinase-9 expression and secretion by parthenolide derivatives.
Semisynthetic derivatives of parthenolide (1) were tested on NF-kB driven transcription and metalloproteinase-9 (MMP-9) expression and secretion. The four membered ring compounds 5 and 6, obtained by acidic treatment of 1, exhibited a higher activity with respect to 1 in all the biological assays. Then an increased ability of the 5 and 6 to inhibit NF-kB driven transcription may lead to a down-regulation of MMP-9 expression and secretion. This work provides new details about the structural requisites for NF-kB inhibition.
Dell'Agli
Mario
M
Department of Pharmacological Sciences, University of Milan, Italy. mario.dellagli@unimi.it
Galli
Germana V
GV
Bosisio
Enrica
E
D'Ambrosio
Michele
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D020128:Inhibitory Concentration 50; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014158:Transcription, Genetic
D003503:Cyclobutanes; D016328:NF-kappa B; D012717:Sesquiterpenes; C002669:parthenolide; D020780:Matrix Metalloproteinase 9; D015107:4-Butyrolactone