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.
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.
Tindal
David J
DJ
Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726, Australia.
Dyason
Jeffrey C
JC
Thomson
Robin J
RJ
Suzuki
Takashi
T
Ueyama
Hiroo
H
Kuwahara
Yohta
Y
Maki
Naoyoshi
N
Suzuki
Yasuo
Y
von Itzstein
Mark
M
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
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid