• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3359-3365
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• 2010

The incorporation of microwave irradiation with the prevalent "click chemistry" is currently of considerable synthetic interest. We describe here the introduction of such laboratorial shortcut into carbohydrate-based drug discovery, resulting in the rapid formation of a series of triazole-linked salicylic $\beta$-D-O-glycosides with biological activities. All "clicked" products were achieved in excellent yields ($\approx$ 90%) within only a quarter. In addition, based on the structural characteristics of the afforded glycomimetics, their inhibitory activities were evaluated toward protein tyrosine phosphatases 1B (PTP1B) and a panel of homologous protein tyrosine phosphatases (PTPs). Docking simulation was also conducted to plausibly propose binding modes of this glycosyl salicylate series with the enzymatic target.

• Bulletin of the Korean Chemical Society
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• v.29 no.5
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• pp.921-927
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• 2008

Discovery of $\alpha$-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate mediated diseases. As a method for the discovery of new novel inhibitors of $\alpha$-glucosidase, we have addressed the performance of the computer-aided drug design protocol involving the homology modeling of $\alpha$-glucosidase and the structure-based virtual screening with the two docking tools: FlexX and the automated and improved AutoDock implementing the effects of ligand solvation in the scoring function. The homology modeling of $\alpha$-glucosidase from baker’s yeast provides a high-quality 3-D structure enabling the structure-based inhibitor design. Of the two docking programs under consideration, AutoDock is found to be more accurate than FlexX in terms of scoring putative ligands to the extent of 5-fold enhancement of hit rate in database screening when 1% of database coverage is used as a cutoff. A detailed binding mode analysis of the known inhibitors shows that they can be stabilized in the active site of $\alpha$- glucosidase through the simultaneous establishment of the multiple hydrogen bond and hydrophobic interactions. The present study demonstrates the usefulness of the automated AutoDock program with the improved scoring function as a docking tool for virtual screening of new $\alpha$-glucosidase inhibitors as well as for binding mode analysis to elucidate the activities of known inhibitors.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.1000-1006
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• 2011

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.