The design, synthesis and biological evaluation of neuraminic acid-based probes of Vibrio cholerae sialidase

Saturation transfer difference (STD) 1H‐NMR experiments and in silico docking experiments to probe the binding of N‐acetylneuraminic acid and derivatives to Vibrio cholerae sialidase

“…The docking results confirm the proximity of Trp311 to the methyl group of the C‐5 acetamide groups of 2 and 3 . The importance of this hydrophobic interaction has previously been noted in an extensive GRID study of the active site of V. cholerae sialidase, and exploration of a series of C‐5 modified Neu5Ac2en derivatives, carried‐out to potentially exploit the favorable hydrophobic characteristics of this region of the active site 36…”

Syntheses of 2-Deoxy-2,3-didehydro-<i>N</i>-acetylneuraminic Acid Analogues Modified by α-Acylaminoamido Groups at the C-4 Position Using Isocyanide-Based Four-Component Coupling and Biological Evaluation as Inhibitors of Human Parainfluenza Virus Type 1

“…Among the diverse array of compounds related to the sialic acid family, 4) 5-acetamido-2,6-anhydro-3,5-dideoxy-d-galacto-d-glycero-non-2-enonic acid (Neu5Ac2en, 1) is known as an inhibitor of sialidases from both bacterial and viral sources, occupying an important position in modern chemistry. 5,6) A variety of Neu5Ac2en analogs have been synthesized as competitive sialidase inhibitors. By molecular modeling techniques, von Itzstein et al reported the design and biological evaluation of 4-deoxy-4-guanidino-Neu5Ac2en analogs (2) (zanamivir).…”

N ‐Acetylneuraminic Acid Derivatives and Mimetics as Anti‐Influenza Agents

“…All X-ray crystallographic structures of sialidases that recognize 5-acetamido sialic acids solved to date have a defined pocket within the active site to accommodate the C-5 acetamido group [100]. The structure of Neu5Ac2en (3) in complex with influenza A (N2) sialidase [53] indicates hydrogen-bonding interactions between the proton on the acetamido nitrogen and a structural water molecule, between the acetamido carbonyl group and conserved Arg152, and potential hydrophobic interactions between the acetamido methyl group and conserved residues Trp178 and Ile222.…”

“…A number of studies have examined the tolerance of bacterial and viral sialidases to changes at C-5 in sialoside substrates [101,102] and in 2,3-dehydrosialic acids as enzyme inhibitors [61,100,103]. For influenza virus sialidase, the modification of Neu5Ac2en that gave the most potent inhibition was replacement of the C-5 acetamido group with a di-or trifluoroacetamido group, which resulted in slightly (fourfold) stronger inhibition than Neu5Ac2en [61].…”