Synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge Aplysinella rhax and its analogues

Yuzo Fujita; Naohiro Ohshima; Ai Hasegawa; Frank Schweizer; Tadahiro Takeda; Fumiyuki Kiuchi; Noriyasu Hada

doi:10.3390/molecules16010637

Synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge Aplysinella rhax and its analogues

Molecules. 2011 Jan 17;16(1):637-51. doi: 10.3390/molecules16010637.

Authors

Yuzo Fujita¹, Naohiro Ohshima, Ai Hasegawa, Frank Schweizer, Tadahiro Takeda, Fumiyuki Kiuchi, Noriyasu Hada

Affiliation

¹ Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

Abstract

The novel glycosphingolipid, β-D-GalNAcp(1-->4)[α-D-Fucp(1-->3)]-β-D-GlcNAcp(1-->)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an α1-->3 and β1-->4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric oxide (NO) production inhibitory activity against LPS-induced J774.1 cells. Our results indicate that both the presence of a D-Fucα1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbohydrate Sequence
Cell Line
Glycosphingolipids / chemical synthesis*
Glycosphingolipids / chemistry
Glycosphingolipids / pharmacology*
Magnetic Resonance Spectroscopy
Marine Biology*
Mice
Molecular Sequence Data
Nitric Oxide / antagonists & inhibitors*
Porifera / chemistry*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structure-Activity Relationship

Substances

Glycosphingolipids
Nitric Oxide