Antifouling activity of bromotyrosine-derived sponge metabolites and synthetic analogues.
Eighteen brominated sponge-derived metabolites and synthetic analogues were analyzed for antilarval settlement of Balanus improvisus. Only compounds exhibiting oxime substituents including bastadin-3 (4), -4 (1), -9 (2), and -16 (3), hemibastadin-1 (6), aplysamine-2 (5), and psammaplin A (10) turned out to inhibit larval settling at 1 to 10 microM. Analogues of hemibastadin-1 (6) were synthesized and tested for structure activity studies. Debromohemibastadin-1 (8) inhibited settling of B. improvisus, albeit at lower concentrations than hemibastadin-1 (6). Both 6 and 8 also induced cyprid mortality. 5,5'-dibromohemibastadin-1 (7) proved to be nontoxic, but settlement inhibition was observed at 10 microM. Tyrosinyltyramine (9), lacking the oxime function, was not antifouling active and was non-toxic at 100 microM. Hemibastadin-1 (6) and the synthetic products showed no general toxicity when tested against brine shrimp larvae. In contrast to the lipophilic psammaplin A (10), the hydrophilic sulfated psammaplin A derivative (11) showed no antifouling activity even though it contains an oxime group. We therefore hypothesize that the compound needs to cross membranes (probably by diffusion) and that the target for psammaplin A lies intracellularly.
Ortlepp
Sofia
S
Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University, Universitätstrasse 1, Geb. 26.23, D-40225 Düsseldorf, Germany.
Sjögren
Martin
M
Dahlström
Mia
M
Weber
Horst
H
Ebel
Rainer
R
Edrada
RuAngelie
R
Thoms
Carsten
C
Schupp
Peter
P
Bohlin
Lars
L
Proksch
Peter
P
D000818:Animals; D001156:Artemia / Q000187:drug effects; D007814:Larva / Q000187:drug effects; D008386:Marine Biology; D010091:Oximes / Q000737:chemistry / Q000633:toxicity; D010647:Phenyl Ethers / Q000737:chemistry / Q000633:toxicity; D011161:Porifera / Q000737:chemistry*; D001468:Thoracica / Q000187:drug effects* / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D010091:Oximes; D010647:Phenyl Ethers; C475724:bromotyrosine; D014443:Tyrosine
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