title: Antifouling activity of synthesized peptide analogs of the sponge metabolite barettin.
abstract: Barettin (cyclo [(6-bromo-8-en-tryptophan) arginine]), a diketopiperazine isolated from the marine sponge Geodia barretti, is a potent inhibitor of barnacle larvae settlement with an EC50-value of 0.9 microM. In the present study, 14 analogs of barettin and its structural congener dipodazine were synthezised and tested for their ability to inhibit larval settlement. Two of the analogs have an intact barettin skeleton. The remaining analogs have a dipodazine skeleton (a diketopiperazine where arginine is replaced with glycine). Six of the tested synthetic analogs displayed significant settlement inhibition with the most potent inhibitor being benzo[g]dipodazine, which displayed even stronger activity than barettin (EC50-value 0.034 microM). The effect of benzo[g]dipodazine was also shown to be readily reversible, when cyprids were transferred to filtered seawater (FSW).
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Sjögren
authors.forename: Ann-Louise
authors.initials: AL
authors.lastname: Johnson
authors.forename: Erik
authors.initials: E
authors.lastname: Hedner
authors.forename: Mia
authors.initials: M
authors.lastname: Dahlström
authors.forename: Ulf
authors.initials: U
authors.lastname: Göransson
authors.forename: Hamid
authors.initials: H
authors.lastname: Shirani
authors.forename: Jan
authors.initials: J
authors.lastname: Bergman
authors.forename: Per R
authors.initials: PR
authors.lastname: Jonsson
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
mesh_terms: D000818:Animals; D054659:Diketopiperazines; D005998:Glycine / Q000138:chemical synthesis / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007814:Larva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D001468:Thoracica / Q000166:cytology / Q000187:drug effects
chemical_list: D054659:Diketopiperazines; D007211:Indoles; D010456:Peptides, Cyclic; D010879:Piperazines; C484472:barettin; C514604:dipodazine; D005998:Glycine