Chemistry Reference
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TABLE 12.1 Glycosidase Inhibitory Activities (Inhibition Constant
K
i,
M) for 1-DNJ
and Its Multivalent Azasugar Derivatives (44-48)
Enzyme
1-DNJ
44
45
46
47
48
- Galactosidase
42
950
±
20
n.i.
n.i.
760
±
10
790
±
10
- Galactosidase
-
120
±
5
95
±
5
215
±
5
105
±
5
225
±
5
- Glucosidase
47
47
±
2
100
±
5
70
±
2 0
±
2
400
±
10
- Glucosidase
25
n.i.
n.i.
n.i.
n.i.
n.i.
- Mannosidase
-
n.i.
n.i.
n.i.
772
±
10
n.i.
- Mannosidase
270
230
±
10
265
±
10
120
±
5 0
±
3
35
±
2
Amyloglucosidase
2.1
28
±
1
30
±
2
17
±
1 0
±
2
11
±
1
n.i.
=
no inhibition detected for 2 mM.
against different glycosidase enzymes have been summarized in Table 12.1 that mani-
fested the absence of any regular variation in activity with valency for all glycosidases
[69].
Our group at CDRI investigated a series of 1,2,3-1
H
-triazolyl glycohybrids con-
taining two or more than two sugar units or a chromenone moiety via CuAAC
reaction of glycosyl azides with 2,3-unsaturated alkynyl glycosides or propargyloxy
coumarins (Fig. 12.18). The synthesized triazoles were screened for
-glucosidase,
glycogen phosphorylase, and glucose-6-phosphatase inhibitory activities, out of
which triazole glycohybrids (
49-52
) demonstrated promising inhibitory activities
(Table 12.2) [10].
Focusing on development of potent
-galactosidase inhibitors of
E. coli
, Kovensky
et al. investigated selective azidation in preparing polyazide derived platform for
the installation of various alkyne substituted 1-thio-
-D-galactosides moieties via
CuAAC reaction. The stability of
S
-linked glycosides toward hydrolytic conditions
and specific affinity of the selected enzyme for galactosides established the alkyne
OH
N
OH
N
O
N
N
N
N
O
O
O
O
O
HO
HO
HO
O
O
HO
CMe
2
OH
O
(CH
2
)
4
CH
3
CH
3
50
49
H
O
O
OH
OH
HO
OH
N
N
N
O
OAc
O
N
N
N
HO
HO
O
O
Ac
AcO
O
(CH
2
)
4
CH
3
OAc
51
52
FIGURE 12.18
1,2,3-1
H
-triazolyl glycohybrids, inhibitors of various glycosidase enzymes.
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