Unprecedented Hemiketal Cembranolides with Anti-inflammatory Activity from the Soft Coral Lobophytum durum

Abstract

Chemical investigations of the soft coral Lobophytum durum have led to the isolation of three unprecedented hemiketal cembranolides, durumhemiketalolides A-C (1-3). Full NMR spectroscopic assignments are provided for all isolated metabolites. The anti-inflammatory activities of 1-3 were evaluated in vitro.

Antibacterial and cytotoxic properties of isoprenoids from the red sea soft coral, <i>Lobophytum</i> sp

“…In a continuing efforts at studying marine metabolites, collected from Red Sea Saudi Arabia, with biological activity, we have previously isolated several bioactive secondary metabolites from Sarcophyton trocheliophorum and S. glaucum [2][3][4][5] Recently, our interest in allcyonaria coral, led us to isolate several secondary metabolites from Lobophytum sp. Literature survey showed that metabolites of Lobophytum sp exhibited various biological activities, such as antitumor [6][7][8][9][10][11][12][13], antibacterial [14], anti-inflammatory activities [14][15][16] and antiviral [17]. Our investigation led to the isolation and characterization of four sesquiterpenes: alismol (1), nardol (2) aristol-9-ene (3), alismoxide (5), one cembranoid type diterpene, cembrene A (4), and two steroid type compounds, Chalinasterol (6) and Nephalsterol C (7).…”

Cembrane Diterpenes Chemistry and Biological Properties

“…Both metabolites 397 and 399 reduced the levels of iNOS to 11.0 ± 1.3% and 0.0 ± 0.0%, respectively, and of COX-2 to 66.7 ± 6.4% and 34.7 ± 4.2%, respectively, in comparison with those of the control groups. Metabolite 398 reduced iNOS protein expression (6.4 ± 0.2%), but did not inhibit COX-2 protein expression [119]. Six new cembranoids, laevigatlactones A-F (400-405) were isolated from leaves of Croton laevigatus.…”

“…Metabolite 115 inhibited the accumulation of the pro-inflammatory iNOS protein of LPS-stimulated RAW264.7 macrophage cells at 50 μM [41]. Four new cembranoid diterpenes, 11,12-epoxy-1(E),3(E),7(E)-cembratrien-15-ol (117), 3,4:11,12-diepoxy-15-methoxy-1(E),7(E)-cembradiene (118), 1(E),3(E),7(E),11(E)-cembratetraene-14,15-diol (119), and 3,14-epoxy-1(E),7(E),11(E)-cembratriene-4,15-diol (120), have been isolated from the soft coral Sinularia gibberosa [42]. A series of analogs were isolated from the soft coral Sinularia flexibilis (121) [43], Sinularia gibberosa (122) [44], Sarcophyton decaryi (123,124) [45,46], Nephthea brassica (125) [47], Lobopbytum pauciflorum (126)(127) [20,48], Sarcophyton mililatensis (130) [49].…”

Marine soft corals as source of lead compounds for anti-inflammatories

“…Similarly, from the same university, Cheng et al found that new cembranolides from the soft coral Lobophytum durum, durumolides A-C (5, 6, 7) inhibited both the iNOS and COX-2 proteins in LPS-activated RAW 264.7 cells in vitro (apparently IC 50 was less than 10 μmol/L) suggesting that the α-methylene-γ-lactone moiety of these compounds was necessary for the observed activity [19]. Cheng et al also isolated durumhemiketalolides A-C (8, 9, 10) and durumolide F (11) from the soft coral Lobophytum durum with anti-inflammatory activity [20,21]. Both compounds 8 and 10 reduced the levels of iNOS to (11.0 ± 1.3)% and (0.0 ± 0.0)%, respectively, and of COX-2 to (66.7 ± 6.4)% and (34.7 ± 4.2)%, respectively.…”

“…Ahmed et al reported that the known steroid gibberoketosterol (20) isolated from the Formosan soft coral Sinularia gibberosa significantly reduced pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated murine macrophages at a concentration of 10 μmol/ L to 44.5% and 68.3% of control values, respectively [27]. Cheng et al isolated chabrosterol (21) and nebrosteroid I (22) from the soft coral Nephthea chabroli which significantly reduced the levels of the iNOS protein (12.4% ± 2.9% and 20.2% ± 2.6%) and COX-2 protein (45.2% ± 5.4% and 75.3% ± 3.3%) (Figure 3) [17].…”