Study On Chemical Constituents And Bioactivities Of Brominated Alkaloids From Two Marine Sponges

Brominated alkaloids are widely existed in marine organisms with novel structure and various biological activities. In this paper, we studied on brominated alkaloids from two marine sponges(Aplysina aerophoba and Axinella verrucosa). According to the mass spectrum characters of brominated compounds, first performed HPLC-MS for the two methanol extracts. Then determined the targeted chromatographic peak (brominated compounds). Colum chromatography on VLC, Sephadex LH-20, silica gel, ODS, MPLC and semi-preparative HPLC were applied for the targeted isolation and purification of the brominated alkaloids. Their structures were determined by spectroscopic analysis including NMR and MS, and by comparison with the data from literatures.From the methanol extract of Aplysina aerophoba, five bromotyrosine-alkaloids were isolated and identified as:benzeneethanaminium (1), (E)-1-acetamide-3,5-dibromo-4-ethoxy-4-methoxy-1-hydroxy-2,5-cyclohexad-dienone (2), (Z)-1-acetamide-3,5-dibromo-4-ethoxy-4-methoxy-1-hydroxy-2,5-cyclohexaddienone (3), benzeneacetamide (4), (R*,S*) [3,5-dibromo-4-[(2-oxo-5-oxazolidinyl)] methoxyphenyl]-2-oxazolidinone (5). Compound 2,3,4 were isolated from the species for the first time. Compound 1 and compound 5 were isolated from the genus for the first time.From the methanol extract of Axinella verrucosa, five bromopyrrole alkaloids were isolated and identified as:hymenidin (6), stevensine (7), 4-bromopyrrole-2-carboxylic acid (8),4,5-dibromopyrrole-2-carboxylic acid (9),3, 5-dibromo-2-pyrrole carboxylic acid (10). Compound 9 was isolated from the species for the first time. Compound 10 was isolated from the genus for the first time.Lymphocyte proliferation assay was made to investigate the immune-modulating activity of the compounds. Some brominated alkaloids showed immune enhancement activity, some showed immune inhibition activity. Benzeneacetamide (4) obtained from Aplysina aerophoba extremely suppressed the proliferation of B-lymphocytes induced by LPS (p<0.01). (R*,S*) [(2-oxo-5-oxazolidinyl)] methoxyphenyl]-2-oxazolidinone (5) remarkably suppressed the proliferation of T-lymphocytes induced by ConA (p<0.05). Hymenidin (6) which obtained from Axinella verrucosa can remarkably increase the proliferation of T-lymphocytes induced by ConA (p<0.05). Stevensine (7) remarkably increased the proliferation of B-lymphocytes induced by LPS (p<0.05). It is the first report for the immunity suppressing activities of compound 4,5 and the immunity enhancing activities of compound 6,7.