Design of N-acetyl-6-sulfo-beta-d-glucosaminide-based inhibitors of influenza virus sialidase.
Biological activity of N-acetyl-6-sulfo-beta-d-glucosaminides (6-sulfo-GlcNAc 1) having a structural homology to N-acetylneuraminic acid (Neu5Ac 2) and 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en 3) was examined in terms of inhibitory activity against influenza virus sialidase (influenza, A/Memphis/1/71 H3N2). pNP 6-Sulfo-GlcNAc 1a was proved to show substantial activity to inhibit the virus sialidase (IC(50)=2.8 mM), though p-nitrophenyl (pNP) GlcNAc without 6-sulfo group and pNP 6-sulfo-GlcNH(3)(+) 1b without 2-NHAc showed little activity (IC(50) >50 mM). The activity was enhanced nearly 100-fold when the pNP group of 1a was converted to p-acetamidophenyl one 5 (IC(50)=30 microM) or replaced with 1-naphthyl 6 (IC(50)=10 microM) or n-propyl one 8 (IC(50)=11 microM).
Sasaki
Kenji
K
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
Nishida
Yoshihiro
Y
Kambara
Mikie
M
Uzawa
Hirotaka
H
Takahashi
Tadanobu
T
Suzuki
Takashi
T
Suzuki
Yasuo
Y
Kobayashi
Kazukiyo
K
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry*; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D012794:Sialic Acids / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012794:Sialic Acids; C035547:glucosaminic acid; D009439:Neuraminidase; D005944:Glucosamine