Design, synthesis, and biological evaluation of human sialidase inhibitors. Part 1: selective inhibitors of lysosomal sialidase (NEU1).
We here report the design and synthesis of selective human lysosomal sialidase (NEU1) inhibitors. A series of amide-linked C9 modified DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) analogues were synthesized and their inhibitory activities against all four human sialidases (NEU1-NEU4) were determined. Structure-based approach was used to investigate the basis of selectivity of the compounds with experimentally observed activity. Results from the present study are found to be informative in a qualitative manner for the further design of isoform selective human sialidase inhibitors for therapeutic value.
Magesh
Sadagopan
S
Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193, Japan. sadmag77@gmail.com
Moriya
Setsuko
S
Suzuki
Tohru
T
Miyagi
Taeko
T
Ishida
Hideharu
H
Kiso
Makoto
M
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D008247:Lysosomes / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D009439:Neuraminidase