title: Synthesis and evaluation of 4-O-alkylated 2-deoxy-2,3-didehydro-N-acetylneuraminic acid derivatives as inhibitors of human parainfluenza virus type-3 sialidase activity.
abstract: The X-ray crystal structure of the paramyxoviral surface glycoprotein haemagglutinin-neuraminidase (HN) from Newcastle Disease virus was used as a template to design inhibitors of the HN from human parainfluenza virus type-3 (hPIV-3). 4-O-Alkylated derivatives of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), accessed from 8,9-O-isopropylidenated-Neu5Ac2en1Me, were found to inhibit the sialidase (neuraminidase) activity of hPIV-3 (strain C243) in the range of 3-30muM. This is comparable or improved activity compared to the parent 4-hydroxy compound.
authors.affiliation: Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tindal
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Thomson
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueyama
authors.forename: Yohta
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Maki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D002460:Cell Line; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D010224:Parainfluenza Virus 3, Human / Q000201:enzymology*; D013050:Spectrometry, Fluorescence
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid