Halipeptins A and B: two novel potent anti-inflammatory cyclic depsipeptides from the Vanuatu marine sponge Haliclona species.

Abstract

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.).

• Authors: A Randazzo, G Bifulco, C Giannini, M Bucci, C Debitus, G Cirino, L Gomez-Paloma
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 123 Issue 44 Pg. 10870-6 (Nov 07 2001) ISSN: 0002-7863 [Print] United States
• PMID: 11686688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Depsipeptides
• Peptides, Cyclic
• halipeptin A
• halipeptin B

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, isolation & purification, pharmacology)
• Depsipeptides
• Dose-Response Relationship, Drug
• Edema (drug therapy)
• Humans
• Leukemia L1210 (drug therapy)
• Male
• Mice
• Microbial Sensitivity Tests
• Nuclear Magnetic Resonance, Biomolecular
• Peptides, Cyclic (chemistry, isolation & purification, pharmacology)
• Porifera (chemistry)
• Protein Conformation
• Spectrometry, Mass, Fast Atom Bombardment
• Stereoisomerism
• Tumor Cells, Cultured (drug effects)