Synthesis and biological evaluation of pharbinilic acid and derivatives as NF-κB pathway inhibitors.
A 7-step synthesis of pharbinilic acid, a member of the gibberellin family of natural products and the first naturally occurring allogibberic acid, is reported. An efficient decarboxylative aromatization reaction enables the synthesis of pharbinilic acid and related analogs for evaluation as modulators of NF-κB activity. Remarkably, one analog displays a 2 μM IC50 in an NF-κB activity assay and inhibits an endogenous NF-κB-regulated pathway.
Department of Chemistry, University of Michigan, 930 North University Ave., Ann Arbor, MI 48109, USA. corinnas@umich.edu.
J R
JR
Annand
P A
PA
Bruno
A K
AK
Mapp
C S
CS
Schindler
D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010165:Palladium / Q000737:chemistry; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects
D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; D053583:Interleukin-1beta; D016328:NF-kappa B; C584228:pharbinilic acid; D010165:Palladium