Chromanols from Sargassum siliquastrum and Their Antioxidant Activity in HT 1080 Cells
Chemical and pharmaceutical bulletin
Note Brown algae of the genus Sargassum are widely distributed in the temperate and tropical oceans of the world, and often dominate benthic algal communities, occurring in huge floating masses. Most species have cycles of vegetative growth and attrition. 1) A number of researchers have reported their biological activities 2-9) as well as secondary metabolites. 10-23) The brown alga S. siliquastrum is commonly found in the coastal area of the Korean peninsula. Recently, some studies have
... ed that S. siliquastrum possesses a number of meroditerpenoids of the chromene and related structural class     and some of these meroditerpenoids exhibit biological activities such as cytotoxicity, antioxidant capacity, vasodilatation, inducement of the larval settlement of the hydrozoan, and inhibition of butylcholine esterase.    In the course of our countinuing search for bioactive compounds from marine algae, the brown alga S. siliquastrum was collected along the offshore of Jeju Island, Korea. Antioxidant activity of its organic extract was evaluated on ROS in cellular system. Bioactivity-guided partitioning and various chromatographic methods resulted in the isolation of several compounds of chromene class. Herein we report structure elucidation of chromanols (1-6), together with three new metabolites (4-6), and their scavenging effect on ROS in HT 1080 cells. Results and Discussion The brown alga Sargassum siliquastrum was collected along the offshore of Jeju Island, Korea. The collected samples were extracted with acetone-CH 2 Cl 2 (1 : 1) and MeOH, respectively. The combined crude extracts of S. siliquastrum were fractionated into n-hexane, 85% aq. MeOH, n-BuOH, and water fractions. The 85% aq. MeOH fraction was subjected to C 18 reversed-phase vacuum flash chromatography using sequential mixtures of MeOH and water as eluents, followed by reversed-phase HPLC to yield six chromanols including new three chromanols (Fig. 1) . The three known chromanols were readily identified as two diastereomeric sargachromanols D (1) and E (2) and sargachromanol K (3) by a combination of spectroscopic analysis and comparison with data reported for these compounds. 24) Two closely related metabolites, 4 and 5, were isolated as a colorless gum. They had the same molecular formula C 27 H 42 O 5 determined by combined high resolution (HR)-FAB mass and 13 C-NMR spectrometry, and were diastereomeric to each other at C-9Ј or C-10Ј as 1 and 2. The NMR spectral data of the former were very similar to those obtained for sargachromanol D (1) while those of the latter were very close to those derived from sargachromanol E (2). Six meroterpenoids (compounds 1-6) of chromene class, including three known compounds (1-3), were isolated from Sargassum siliquastrum. The structure of these compounds was established by extensive 2D-NMR experiments such as 1 H gradient double quantum filtered correlation spectroscopy (gDQCOSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), gradient heteronuclear multiple quantum coherence (gHMQC), and gradient heteronuclear multiple bond correlation (gHMBC), and by comparison with published spectral data. The antioxidant activity of these compounds was evaluated by various antioxidant tests, such as scavenging effects on generation of intracellular reactive oxygen species (ROS), increments of intracellular glutathione (GSH) level, and inhibitory effects on lipid peroxidation in human fibrosarcoma HT 1080 cells. Compounds (1-6) significantly decreased generation of intracellular ROS and inhibited lipid peroxidation while they increased levels of intracellular GSH at a concentration of 5 m mg/ml.