Secondary metabolites from three Florida sponges with antidepressant activity

Abstract

Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety-depression continuum model. Among the isolated compounds, 5,6-dibromo- N,N-dimethyltryptamine ( 1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo- N,N-dimethyltryptamine ( 2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs.

Figure 1

Reduction of immobility time in the forced swim test by 5,6-dibromo-N,N-dimethyltryptamine (1).

Figure 2

Effects of 5,6-dibromo-N,N-dimethyltryptamine (1) on separation distress vocalization rates during the anxiety phase (0 to 5 min, panel A) and the depression phase (30 to 120 min, panel B) of the test session. * indicates a significant decrease (i.e., anxiolytic effect) and ** indicates a significant increase (i.e., antidepressant effect) of vocalization rate compared to vehicle-treated chicks. All p^s < 0.05.

Figure 3

Effect of compounds 3 (AP), 2 (BDT), and 4 (ili-maquinone) in (A) forced swim test and (B) locomotor activity test in male Swiss Webster mice. *p < 0.05 and ***p < 0.001 versus corresponding vehicle.