Azorellane diterpenoids from Laretia acaulis inhibit nuclear factor-kappa B activity.
Transcription factor NF-kappaB plays a key role in the inducible expression of genes mediating proinflammatory effects, and is thus an important target for the development of antiinflammatory drugs. Laretia acaulis (Cav.) Gill et Hook (Apiaceae) is a medicinal plant used in the high Andes mountains for different ailments such as diabetes, inflammation and for general pain. In addition to the known azorellanol (2) and 7-deacetylazorellanol (4), 13-epiazorellanol (1) was also isolated from the aerial part of this plant. Its structure was based on spectroscopic comparison with azorellanol (2) and by chemical characterization. While compounds 2 and 4 showed potent anti-NF-kappaB activity by targeting the activity of the IkappaBalpha kinase, compound 1 was completely inactive highlighting the importance of position 13 in the biological activities of this class of tetracyclic diterpenoids.
Borquez
Jorge
J
Laboratory of Natural Products, Department of Chemistry, Faculty of Basic Sciences, University of Antofagasta, Antofagasta, Chile. jborquez@uantof.cl
Loyola
Luis A
LA
Morales
Glauco
G
San-Martín
Aurelio
A
Roldan
Raquel
R
Marquez
Nieves
N
Muñoz
Eduardo
E
D019661:Apiaceae / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification*; D006801:Humans; D019169:Jurkat Cells; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004224:Diterpenes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha