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OH
O
H
CO
2
H
HO
HO
H
O
O
COOH
OH
O
H
AcHN
HO
N
CO
2
H
HO
N
N
OH
HO
O
AcHN
N
AcHN
N
N
N
HO
N
N
O
O
H
CO
2
H
SPh
( )
7
HO
34
O
CH
C
2
H
5
OH
HO
33
35
OH
AcNH
OH
HO
OH
O
CO
2
H
OH
HO
O
H
CO
2
H
N
O
N
N
N
N
HO
N
O
O
O
HO
2
C
O
C
O
2
H
HO
O
H
HO
N
N
OH
O
H
O
O
N
N
AcHN
OH
N
N
HO
36
HO
NHAc
FIGURE 12.14
Sialic acid based potent neuraminidase inhibitors.
click chemistry. Among the synthesized neuraminidase inhibitors, the compound (
33
)
with an IC
50
value of 6.4
M exhibited anti-AIV activity as compared to zanamivir
(IC
50
=
M), the reference drug [58].
Linhardt et al. prepared a library of 1,2,3-triazoles of sialic acid using CuAAC
reaction of methyl-[5-acetamido-3,5-dideoxy-2-azido-D-glycero-
2.8
-D-galacto-non-
2-ulopyranoside]onate with terminal alkyne functionalized molecules and screened
them for neuraminidase inhibitory activity (Fig. 12.14). The click reaction of com-
pound sialyl azide with dec-1-yne afforded 5-acetamido-3,5-dideoxy-2-(4-octyl-1
H
-
1,2,3-triazol-1-yl)-D-glycero-
-D-galacto-non-2-ulopyranosidic acid (
34
), a poten-
tial lead having neuraminidase inhibitory activity (IC
50
value of 28
M) comparable
to the known sialidase inhibitor Neu5Ac2en. Similarly, sialic acid disaccharide mimic
(
35
)(IC
50
=
17
M) and dendrimer (
36
) (IC
50
=
20
M) demonstrated significant
neuraminidase inhibitory activity (Fig. 12.14) [59].
12.5.5 Miscellaneous Activities
A diverse range of physiological and pathological processes that involve rupture or
the construction of glycosidic linkages can be regulated by identifying inhibitors of
glycosidases and glycosyl transferases that catalyze these processes. Therefore, they
may serve as highly promising therapeutic agents for the treatment of diseases such as
diabetes [60,61], viral infections [62,63] or cancer metastasis [64]. The 1,2,3-triazoles
are poorly basic in nature and as a result remain non-protonated under physiological
pH. Studies have revealed that the nonprotonated sp
2
-hybridized nitrogen atoms of
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