Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 469–476
Comparative evaluation of
D
-glucosyl thiouronium, glucosylthio
heterocycles, Daonil, and insulin as inhibitors for hepatic
glycosidasesq
Olfat M. El din Awad,a Wafaa E. Attiab and El Sayed H. El Ashryb,*
aDepartment of Biochemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt
bDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria 21321, Egypt
Received 14 April 2003; accepted 7 November 2003
Dedicated to Prof. Hassan S. El Khadem for his achievements on the occasion of his 80th birthday
Abstract—Comparison of the in vivo and in vitro effects of S-(2,3,4,6-tetra-O-acetyl-b-
D
-glucopyranosyl)thiuronium bromide (1),
-glucopyranosyl-
2-(2,3,4,6-tetra-O-acetyl-b- -glucopyranosylthio-1,3,4-thiadiazolin-5-thione (2), and 2-(2,3,4,6-tetra-O-acetyl-b-
D
D
thio)-1,3-benzoxazole (3), as well as the antidiabetics Daonil and insulin on glycosidase enzymes has been investigated. Compound 1
inhibited both a- and b-glucosidases, but the inhibition was more potent with the b-enzyme. Compound 2 was found to be a weaker
inhibitor of these enzymes, while compound 3 showed a slight apparent activation.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Keywords: a-Glucosidase; b-Glucosidase; Glucopyranosylthio; Thiouronium; Thiadiazolinthione; Benzoxazole
1. Introduction
A number of thio sugar derivatives, thioglycosides,
thio-linked oligosaccharides, glycosylamines, and het-
erocycles linked to polyols have shown potential value
as inhibitors.5–25 Here we explore glycosidase inhibition
by new compounds having in common a glucosylthio
moiety attached to carbon linked to nitrogen either in an
open chain (isourea) or cyclic form (heterocyclic ring).
The present study evaluates, S-(2,3,4,6-tetra-O-acetyl-b-
Glycosidase enzymes play various important roles in
biological processes,1–3 and consequently modifying or
blocking such processes are important for therapeutic or
biotechnological applications.1–10 The inhibitors of such
processes may exert their effects by mimicking the
enzymeÕs normal substrate and/or based on their topo-
logical resemblance to the postulated transition state.
Various inhibitors have been used for the treatment of
diabetics, obesity, and hyperlipoproteinemia, as antivi-
rals, particularly against HIV (the causative agents in
AIDS), inhibitors of tumor metastasis, antibacterials,
and insect antifeedants.5–7 The design of glycosidase
inhibitors with a high degree of specificity and potency,
thus ideal inhibitors, has attracted much attention dur-
ing the last few years, and there is still a need for design
and exploration of new lead inhibitors.1–25
D
-glucopyranosyl)thiuronium bromide (1),26 2-(2,3,4,6-
tetra-O-acetyl-b- -glucopyranosylthio)-1,3,4-thiadiaz-
olin-5-thione (2),27 and 2-(2,3,4,6-tetra-O-acetyl-b-
D
D
-
glucopyranosylthio)-1,3-benzoxazole (3)28 (Fig. 1) as
glycosidase inhibitors, and compares their effects with
those of the clinically used antidiabetics. 1-[4-(2-chloro-
2-methoxybenzamido)ethylbenzenesulfonyl]-3-cyclo-
hexyl urea (Daonil)29 and insulin.
2. Results and discussion
Low concentrations of compounds 1, 2, and Daonil had
no significant effect in vitro on the activity of a-gluco-
sidase in the liver homogenate of mice but higher
qAbstracted from the Ph.D. thesis of W.E.A. in biochemistry.
* Corresponding author. Tel.: +3-4201-360; fax: +20-3-4271360/3-4201-
0008-6215/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2003.11.009