Synthesis, Inhibitory Effects on Nitric Oxide and Structure-Activity Relationships of a Glycosphingolipid from the Marine Sponge Aplysinella rhax and Its Analogues

Molecules

Yuzo Fujita¹  Naohiro Ohshima¹  Ai Hasegawa¹  Frank Schweizer¹  Tadahiro Takeda¹  Fumiyuki Kiuchi¹ 

[1] ¹Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. ²Department of Chemistry and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada

关键词: glycosphingolipid;    Aplysinella rhax;    D-fucose;    nitric oxide;   

DOI  :  10.3390/molecules16010637

来源: mdpi

【 摘 要 】

The novel glycosphingolipid, b-D-GalNAcp(1®4)[a-D-Fucp(1®3)]-b-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 a1®3 and b1®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-Fuca1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.