Halipeptins A and B: two novel potent anti-inflammatory cyclic depsipeptides from the Vanuatu marine sponge Haliclona species.
Two new metabolites, named halipeptins A and B, have been isolated from the marine sponge Haliclona sp. Their structures were determined by extensive use of one- and two-dimensional NMR experiments, mass spectrometry, and UV and IR spectroscopy. Halipeptin A is a novel 17-membered cyclic depsipeptide, consisting of five residues including two alanines (with L stereochemistry) and three new residues that appear to be previously undescribed from natural sources: 1,2-oxazetidine-4-methyl-4-carboxylic acid, 3-hydroxy-2,2,4-trimethyl-7-methoxydecanoic acid (HTMMD), and N-methyl-delta-hydroxyisoleucine. The HTMMD residue is substituted with 3-hydroxy-2,2,4-trimethyl-7-hydroxydecanoic acid in halipeptin B. Halipeptin A was found to possess very potent anti-inflammatory activity in vivo, causing about 60% inhibition of edema in mice at the dose of 300 microg/kg (i.p.).
Randazzo
A
A
Dipartimento di Scienze Farmaceutiche, via Ponte don Melillo, Università degli Studi di Salerno, 84084 Fisciano (Salerno), Italy.
Bifulco
G
G
Giannini
C
C
Bucci
M
M
Debitus
C
C
Cirino
G
G
Gomez-Paloma
L
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*; D011487:Protein Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047630:Depsipeptides; D010456:Peptides, Cyclic; C444504:halipeptin A; C444503:halipeptin B