Polysulfated sialic acid derivatives as anti-human immunodeficiency virus.
We report the synthesis of a novel alkyl polysulfated sialic acid derivative denoted as NMSO3. NMSO3 exhibited potent inhibition against both laboratory and clinical human immunodeficiency virus type 1 (HIV-1). The anti-viral activity of this compound (1 uM) was compared to dextran sulfate (3 uM), and was found to be more potent against HIV-1IIIb than AZT (10 uM). The anti-coagulation time was more than 15-fold shorter than that of dextran sulfate. An in vivo anti-viral study of NMSO3 in NOD-SCID-PBL mice HIV model showed complete protection of the animals from virus challenge at the concentration of 10 mg/kg. This suggests that NMSO3 can be effective in the treatment of HIV-infected individuals.
Terada
Masaki
M
Central Research Institute, Nissin Food Products Co. Ltd., 2247 Noji-cho, Kusatsu-city, Shiga 525-0055, Japan. macterad@bc4.so-net.ne.jp
Fujita
Shuji
S
Suda
Isao
I
Mastico
Robert
R
D000478:Alkylation; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008055:Lipids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D008252:Macaca fascicularis; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D012794:Sialic Acids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
C413863:(2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate; D019380:Anti-HIV Agents; D000925:Anticoagulants; D016655:HIV Core Protein p24; D008055:Lipids; D012794:Sialic Acids; D015215:Zidovudine; D016264:Dextran Sulfate; D019158:N-Acetylneuraminic Acid