A potential CARB-pharmacophore for antineoplastic activity: Part 1

Witczak, Zbigniew J.; Popławski, Tomasz; Czubatka, Anna; Sarnik, Joanna; Tokarz, Paweł; VanWert, Adam L.; Bielski, Roman

doi:10.1016/j.bmcl.2014.02.036

Cited by 20 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of sulfur in thio-sugars make them resistant to glycosidases, phosphorylases and glycosyltransferases. There have been some reports [ 18 , 19 ] showing the ability of thio-sugars to impede cancer cell growth. It was shown that functionalized thio-sugars have cytotoxic properties and therapeutic potential as anticancer agents [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

View full text Add to dashboard Cite

Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In a recent screening of various classes of sugars (thio‐, anhydro‐, and sulfamido‐sugars and myo‐inositol oxide), synthesized and studied for cytotoxicity against human cancer cell lines, some sulfur‐containing compounds were found to be promising for future developments due to antineoplastic activity . In particular, compound 87 to 90 (Figure ) were assessed for cytotoxicity and apoptosis against human cancer cell lines (A549, LoVo, MCF‐7, and HeLa) .…”

Section: Endocyclic Oxygen Replacementmentioning

confidence: 99%

Design and synthesis of glycomimetics: Recent advances

Tamburrini

Colombo

Bernardi

2019

Medicinal Research Reviews

View full text Add to dashboard Cite

In the past few decades, our understanding of glycan information‐encoding power has notably increased, thus leading to a significant growth also in the design and synthesis of glycomimetic probes. Combining data from multiple analytical sources, such as crystallography, nuclear magnetic resonance spectroscopy, and other biophysical methods (eg, surface plasmon resonance and carbohydrate microarrays) has allowed to shed light on the key interaction events between carbohydrates and their protein‐targets. However, the low metabolic stability of carbohydrates and their high hydrophilicity, which translates in low bioavailability, undermine their development as drugs. In this framework, the design of chemically modified analogues (called carbohydrate mimics or glycomimetics) appears as a valid alternative for the development of therapeutic agents. Glycomimetics, as structural and functional mimics of carbohydrates, can replace the native ligands in the interaction with target proteins, but are designed to show enhanced enzymatic stability and bioavailability and, possibly, an improved affinity and selectivity toward the target. In the present account, we specifically focus on the most recent advances in the design and synthesis of glycomimetics. In particular, we highlight the efforts of the scientific community in the development of straightforward synthetic procedures for the preparation of sugar mimics and in their preliminary biological evaluation.

show abstract

“…Substitution of the glycosidic oxygen atom with sulfur [35–37] or carbon [38,39] is a now common method to enhance stability of glycosides. Substitution of the pyranose oxygen, such as in 5- S glycosides, can possibly minimize structural changes [40] and such sugar mimics have shown increased cytotoxic activity towards cancer cell lines compared to their O counterpart [41]. Similarly, substitution of the ring oxygen with carbon shows increased stability and lower clearance in vivo [42].…”

Section: Non-natural Sugars To Enhance Glycoside Stabilitymentioning

confidence: 99%

Designing sugar mimetics: non-natural pyranosides as innovative chemical tools

Saliba

Pohl

2016

Current Opinion in Chemical Biology

View full text Add to dashboard Cite

The importance of oligosaccharides in myriad biological processes are becoming increasingly clear. However, these carbohydrate-mediated processes are often challenging to dissect due to the often poor affinity, stability and selectivity of the oligosaccharides involved. To circumvent these issues, non-natural carbohydrates—carbohydrate mimics—are being designed as innovative tools to modify biomolecules of interest or to understand biological pathways using fluorescence microscopy, X-ray or nuclear magnetic resonance spectroscopy (NMR). This review focuses on key examples of recently developed non-natural sugars to answer specific biological needs.

show abstract

A potential CARB-pharmacophore for antineoplastic activity: Part 1

Cited by 20 publications

References 24 publications

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives

Design and synthesis of glycomimetics: Recent advances

Designing sugar mimetics: non-natural pyranosides as innovative chemical tools

Contact Info

Product

Resources

About