Antibiotic and cytotoxic activity of brominated compounds from the marine sponge Verongia aerophoba.
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 aerophobin-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) micrograms/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 microM 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 microM) was comparable to that of the clinically used anticancer drug cisplatin (0.7 microM).
Teeyapant
R
R
Julius-von-Sachs-Institut für Biowissenschaften, Lehrstuhl für Pharmazeutische Biologie, Universität Würzburg, Bundesrepublik Deutschland.
Woerdenbag
H J
HJ
Kreis
P
P
Hacker
J
J
Wray
V
V
Witte
L
L
Proksch
P
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000302:isolation & purification* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011161:Porifera; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006842:Hydrocarbons, Brominated