STAT-3 Inhibitory Bisabolanes from Carthamus glaucus

Abstract

Apart from a large amount (ca. 2.0%) of α-bisabolol β-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 [(-)-α-bisabolol, 1], an anti-inflammatory cosmetic ingredient in current short supply in its natural form. A comparative investigation of the activity of α-bisabolol (1a), the fucopyranoside 2a, and its senecioate 2b on transcription factors involved in inflammation and cancer pathways (NF-κB and STAT-3) showed only marginal activity on NF-κB inhibition for all compounds, while STAT-3 was inhibited potently by the fucoside 2a and, to a lesser extent, also by α-bisabolol. These observations qualify 2a as an easily available compound, both as an apoptotic lead structure and as a potential alternative to natural α-bisabolol (1) for pharmaceutical and/or cosmetic development.

Peroxy natural products

“…192 Another species of the genus, C. glaucus, contained two bisabolane fucopyranosides 339 and 340. 193 Another bisabolene derivative 341 was found from the aerial parts of Achillea clavennae. 194 A germacranolide peroxide 342 was identified as a component of mulgedium tataricum.…”

Natural products and their derivatives regulating the janus kinase/signal transducer and activator of transcription pathway

“…In 2012, compound 20 from Arthamus glaucus is found to have a good inhibitory of STAT3 transcriptional activity with the IC 50 value 6.3 mM in HeLa cell [31]. A phytochemical study on the flower buds of Lonicera japonica yielded four new compounds.…”

Boronic Acid-Catalyzed Final-Stage Site-Selective Acylation for the Total Syntheses of <i>O</i>-3′-Acyl Bisabolol β-D-Fucopyranoside Natural Products and Their Analogues

“…In fact, according to a study on the structure-activity relationship of glycosidic α-bisabolol derivatives, α-bisabolol α-L-ramnoside exhibited a better physicochemical and pharmacokinetic profile compared with α-bisabolol. 32) More recently, α-bisabolol β-D-fucopyranoside 3 33) isolated from Carthamus lanatus has exhibited acecylcholin esterase (AChE) inhibitory activity, antioxidant capacity, antiaggregation, and disaggregation property of amyloid β (Aβ), which is attracting attention as a promising multitarget agent for the treatment of Alzheimer's disease 34) (Fig. 1).…”