Tedanol: a potent anti-inflammatory ent-pimarane diterpene from the Caribbean Sponge Tedania ignis.
Tedanol, a new brominated and sulfated pimarane diterpene was isolated from the Caribbean sponge Tedania ignis. Structure of tedanol was elucidated by mass spectroscopy and extensive NMR studies (including spectral simulation), and its absolute configuration was determined using the Mosher method. Tedanol showed a potent anti-inflammatory activity at 1mg/kg evaluated in vivo in a mouse model of inflammation. After a single intraperitoneal administration, tedanol significantly reduced both the acute and the subchronic phases of carrageenan-induced inflammation. The anti-inflammatory activity was coupled with a strong inhibition of COX-2 expression, inhibition of cellular infiltration measured as mieloperoxidase (MPO) levels, and inhibition of iNOS expression. These features make tedanol a promising template for the development of new anti-inflammatory molecules with low gastrointestinal toxicity.
Costantino
Valeria
V
Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, 80131 Napoli, Italy. valeria.costantino@unina.it
Fattorusso
Ernesto
E
Mangoni
Alfonso
A
Perinu
Cristina
C
Cirino
Giuseppe
G
De Gruttola
Luana
L
Roviezzo
Fiorentina
F
D045784:Abietanes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D011161:Porifera / Q000737:chemistry*
D045784:Abietanes; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; D004791:Enzyme Inhibitors; C545777:tedanol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2