STAT-3 inhibitory bisabolanes from Carthamus glaucus.
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.
Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli Federico II, Via Montesano 49, 80131 Napoli, Italy. scatagli@unina.it
Orazio
O
Taglialatela-Scafati
Federica
F
Pollastro
Lavinia
L
Cicione
Giuseppina
G
Chianese
Maria Luz
ML
Bellido
Eduardo
E
Munoz
Hasan Çetin
HÇ
Özen
Zuhal
Z
Toker
Giovanni
G
Appendino
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031178:Carthamus / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D016328:NF-kappa B / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D050796:STAT3 Transcription Factor / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014421:Turkey
D000893:Anti-Inflammatory Agents; D000081222:Monocyclic Sesquiterpenes; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D012717:Sesquiterpenes; C004497:bisabolol