Synthesis and biological activities of glycosphingolipid analogues from marine sponge Aplysinella rhax.
A novel glycosphingolipid, beta-D-GalNAcp(1-->4)[alpha-D- Fucp(1-->3)]-beta-D-GlcNAcp(1-->)Cer (1), isolated from the marine sponge Aplysinella rhax, has a unique structure, with D-fucose and N-acetyl-D-galactosamine attached to a reducing-end N-acetyl-D-glucosamine through an alpha1-->3 and beta1-->4 linkage, respectively. We synthesized glycolipid analogues carrying a 2-branched fatty alkyl residue or a 2-trimethylsilyl ethyl residue in place of ceramide (2 and 3), non-natural type trisaccharide analogue containing an L-fucose residue (4), and other analogues (5 and 6). Among these prepared compounds, 2 showed the most potent nitric oxide (NO) production inhibitory activity against LPS-activated J774.1 cells. In addition, their structure-activity relationships were established.
Hada
Noriyasu
N
Kyoritsu University of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. hada-nr@kyoritsu-ph.ac.jp
Nakashima
Taishi
T
Shrestha
Suraj Prakash
SP
Masui
Ryo
R
Narukawa
Yuji
Y
Tani
Kayoko
K
Takeda
Tadahiro
T
D000818:Animals; D002240:Carbohydrate Sequence; D002460:Cell Line; D006028:Glycosphingolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011161:Porifera / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization