In the Search of Glycoside-Based Molecules as Antidiabetic Agents

Abstract

This review is an effort to summarize recent developments in synthesis of O -glycosides and N -, C -glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O -glycosides used in the treatment of diabetes are presented, followed by the N -glycosides and finally the C -glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C -Glycosyl compounds mimicking O -glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C -glycosides. Also N -glycosides such as N -(β- d -glucopyranosyl)-amides, N -(β- d -glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5 . In Sect. 6 , biological mechanisms of action of the glycosides and patents of marketed drugs are described.

Influence of Brewer’s Spent Grain Compounds on Glucose Metabolism Enzymes

“…GPα inhibition appeared to be uncorrelated with TFC and TPC. However, given the potent inhibitory activity of the extracts (especially A5 and A7, which was around 10 times that of caffeine) BSG seems to be a potent source of GPα inhibitors [ 61 ]. As the enzyme has seven binding sites, it has many potential targets for allosteric modulation that can accommodate a wide range of chemical structures.…”

Synthesis of sp2-Iminosugar Selenoglycolipids as Multitarget Drug Candidates with Antiproliferative, Leishmanicidal and Anti-Inflammatory Properties

“…The symmetric selenodigalactoside 3 behaves as a relevant ligand for human galectins [15], whereas α-Se-galactosyl ceramide 4 [16], a mimetic of the powerful immunostimulant glycolipid α-galactosyl ceramide (KRN7000) [17], shows interest as a potential adjuvant. In general terms, substitution of the glycosidic oxygen atom by Se results in conjugates that are more robust against enzymatic and chemical degradation, as is also the case with other heteroatoms, such as N or S, empowering the synthesis and biological evaluation of valuable glycomimetics [18][19][20][21][22]. The majority of available methods for the synthesis of X-glycosides (X = heteroatom other than oxygen) mainly afford the β-anomer or α,β-anomeric mixtures [23][24][25][26], the stereoselective synthesis of α-anomers being consistently more demanding [27][28][29].…”

Combined Ultrahigh Pressure Extraction and High-Speed Counter-Current Chromatography for Separation and Purification of Three Glycoside Compounds from Dendrobium officinale Protocorm

“…Glycoside compounds are derivatives of polysaccharides and play an important role in the treatment of liver diseases [ 16 ] and diabetes [ 17 ], and they have anti-tumor [ 18 ] and neuroprotective effects [ 19 , 20 ]. However, the separation of these compounds has always been a major problem in natural medicinal chemistry research because of their highly polarity-sensitive property.…”