STAT-3 Inhibitory Bisabolanes from Carthamus glaucus

Apart from a large amount (ca. 2.0%) of alpha-bisabolol beta-D-fucopyranoside (2a), the aerial parts of the Mediterranean weed Carthamus glaucus afforded an unusual triglyceride (E-2-crotonyl-1,3-distearolylglycerol, 7), two lipophilic flavonoids (6a,b), and a series of bisabolane fucopyranosides variously acylated on the sugar moiety (2b-e) or oxidized on the terpenoid core (3, 4a,b, 5a,b). The fucopyranoside 2a is more soluble in polar media and more versatile in terms of formulation than its aglycone [(-)-alpha-bisabolol, 1], an anti-inflammatory cosmetic ingredient in current short supply in its natural form. A comparative investigation of the activity of alpha-bisabolol (1a), the fucopyranoside 2a, and its senecioate 2b on transcription factors involved in inflammation and cancer pathways (NF-kappa B and STAT-3) showed only marginal activity on NF-kappa B inhibition for all compounds, while STAT-3 was inhibited potently by the fucoside 2a and, to a lesser extent, also by a-bisabolol. These observations qualify 2a as an easily available compound, both as an apoptotic lead structure and as a potential alternative to natural a-bisabolol (1) for pharmaceutical and/or cosmetic development.