Antibiotic and Cytotoxic Activity of Brominated Compounds from the Marine Sponge Verongia aerophoba

Abstract

Analysis of the marine sponge Verongia aerophoba from the Canary Islands afforded eight brominated secondary metabolites including the small molecular weight compounds aeroplysinin-1 (5) and the dienone (7) which were previously shown to arise by enzymatically catalyzed degradation of aerophobin-2 (4) and isofistularin-3 (1) following breakdown of the cellular compartmentation of the sponge. All compounds were identified from their NMR and mass spectra. Aeroplysinin-1 as well as dienone which arise from isofistularin-3 or aeropho­ bin-2 by biotransformation within the sponge showed a significantly higher antibiotic as well as cytotoxic activity than their biogenetic precursors. Antibiotic activity was studied with re­spect to several gram-positive and gram-negative bacteria including B. subtilis, S. aureus and E. coli. The MICs (MBCs) of aeroplysinin-1 (5) and the dienone (7) varied between 12.5-25 (50-100) μg/ml respectively. Cytotoxicity was tested in vitro towards HeLa cells, a human cervix uteri tumour cell line. Aeroplysinin-1 (5) and the dienone (7) displayed pronounced cytotoxic activity with IC50s of 3.0 and 3.2 μм respectively. A five-fold increase in cytotoxicity was observed after O-acetylation of the dienone (7). The IC50 of the dienone O-acetate (0.6 μм) was comparable to that of the clinically used anticancer drug cisplatin (0.7 μм).

The Marine Bromotyrosine Derivatives

“…Many of the bromotyrosine derivatives exhibited cytotoxicity, emphasizing the ecological relevance of this type of compounds in the sponge's chemical defense. The small molecules, aeroplysinin-1 (14) and the dienone 1, which are from the enzymatic degradation of larger bromotyrosine derivatives such as isofistularin-3 (80), aerophobin-2 (114), fistularin-1 (94), and other alkaloids, are more toxic than the parent compounds, suggesting a wound defense reaction (250,263,264).…”

Crystal structure of 5-methoxy-N′-[(3Z)-1-benzyl-5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-1H-indole-2-carbohydrazide-DMSO (1/1), C27H25FN4O4S

“…Isatin (1H-indol-2,3-dione) is an endogenous compound recognized in many organisms and it exhibited a broad spectrum of pharmacological activities [1][2][3][4]. Therefore, it has been extensively utilized for the construction of a variety of compounds showing diverse biological activities [5].…”

Chemical Defenses of Cryptic and Aposematic Gastropterid Molluscs Feeding on their Host Sponge Dysidea granulosa

“…Studies in chemical ecology show that opisthobranchs sequester secondary metabolites from prey, accumulate, concentrate, and distribute them in their tissues, and use them for their own defense (Carte and Faulkner, 1983;Paul et al, 1990;Becerro et al, 2001Becerro et al, , 2003. This strategy of sequestration, concentration, modification, and distribution of metabolites from the prey into the body of the predator is found widely in nudibranchs (Cimino and Ghiselin, 1999 and references therein), sacoglossans (Cimino and Ghiselin, 1998;Becerro et al, 2001), notaspideans (Teeyapant et al, 1993;Ebel et al, 1999;Becerro et al, 2003), and sea hares (Johnson and Willows, 1999). D. granulosa is a chemically defended sponge that produces a number of polybrominated diphenyl ethers (Becerro and Paul, 2004).…”