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In-Depth Information
O
N
NH
O
O
N
NH
2
O
P
O
P
O
N
O
O
O
O
N
H
N
n
N
OH
OH
n = 4
μ
α
IC
50
= 0.15 M ( -1,3-FucT VI)
21
FIGURE 12.8
Triazole synthesis in microtiter plate for
in situ
screening of Fucosyltrans-
ferase VI inhibitor.
IC
50
value of 0.15
M demonstrated specific optimum inhibition for human R-1,3-
fucosyltransferase VI (Fuc-T VI) enzyme (Fig. 12.8) [48].
Presence of more triazole branching units and multivalent glycopyranoside units
generally enhance the anti-inflammatory properties of dendrimers, and indeed the
higher generation dendrimers exhibit better anti-inflammatory activity than the lower
generation. Rajakumar and Anandhan successfully utilized alkyne-azide click reac-
tion in the development of glycodendrimers (
22
) (Fig. 12.9) containing 12 and 18
-D-
glycopyranosides at the periphery, and triazole as branching unit. In anti-inflammatory
assay, the glycodendrimer (
22
) demonstrated significant activity [49].
12.5.2 Antituberculosis Agent
Tuberculosis (TB), caused by
Mycobacterium tuberculosis
, is one of the major causes
of death and suffering worldwide. Directly observed therapy short-course (DOTS), a
World Health Organization (WHO)-approved treatment for TB, involves a three- or
four-drug regimen that comprises isoniazid, rifampin, pyrazinamide, and/or etham-
butol for a minimum of 6 months. However, the increasing microbial resistance,
toxicity, and side effects of currently used anti-tuberculosis drugs also emphasize the
urgent need for the development of more effective anti-tuberculosis agents [50].
The mycobacterial
-(1,6)-mannosyltransferase enzyme plays a key role in
biosynthesis of the cell envelope of
Mycobacterium tuberculosis
, therefore devel-
opment of inhibitors to this enzyme would effectively combat tuberculosis. Don-
doni and coworkers synthesized a new class of (1,6)-oligomannose analogs having
triazole bridges using click chemistry. Ethynyl
-
C
-mannoside upon 1,3 dipolar
coupling with alkyl 6-azido-
-
C
-mannoside derivatives furnished linear oligomers
(triazolo-pentamannose derivative) in good yield [51]. Moreover, a number of
triazole-linked 1,6-oligomannosides up to a hexadecamer (
23
) were also prepared
by the Cu(I)-catalyzed azide-alkyne cycloaddition. Among all, the hexamanno-
side and octamannoside with IC
50
values ranging between 0.14 mM and 0.22 mM
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