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Advances in Glyco-Based Anticancer Agents

A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Biochemistry".

Deadline for manuscript submissions: 28 February 2027 | Viewed by 1217

Editor


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Guest Editor
CEDECOR (UNLP-CICBA), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina
Interests: carbohydrates; medicinal chemistry; enzyme inhibitors; cancer; neglected diseases

Special Issue Information

Dear Colleagues,

In the 1930s, Otto Warburg demonstrated that cancer cells show high rates of glucose cell uptake and secretion of lactic acid, a unique feature of cancer cells, even in the presence of oxygen. This phenomenon, now known as the Warburg effect or aerobic glycolysis, stands out as a distinctive feature across various tumor types. In recent years, several strategies focused on the energy metabolism of cancer cells, leading to targeted treatments against cancer. Due to this increased metabolism, several enzymes and transporters (carbonic anhydrases, glucose transporters, kinases, etc.) are overexpressed in the development of tumor cells. It has been demonstrated that the inhibition of these targets related to glycolysis could become a feasible strategy for cancer treatment. One of the most successful approaches for the design of enzyme and transporter inhibitors involves the attachment of carbohydrate moieties to pharmacophores, leading to the development of novel glycoinhibitors and modulators. Carbohydrates can modify the physicochemical properties of these pharmacological agents. In addition, the stereochemical diversity across the carbohydrate moieties provides an opportunity to interrogate subtle differences in the interaction with the selected targets.

Therefore, authors are invited to submit original research and review articles addressing the progress and current status of the design of glycol-inhibitors and modulators targeting the Warburg effect in cancer.

Topics include, but are not limited to:

  • Natural and synthetic glycosides that target energy metabolism in cancer;
  • Studies of glycosides as antitumor agents (in vitro and in vivo);
  • Docking simulations of known and novel glycosides that interact with targets involved in the Warburg effect.

Prof. Dr. Pedro Colinas
Guest Editor

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Keywords

  • carbohydrates
  • cancer
  • Warburg effect
  • glycolysis
  • enzyme inhibitors
  • transporters inhibitors
  • docking simulations
  • tumor microenvironment

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Published Papers (1 paper)

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Research

17 pages, 2003 KB  
Article
Glycosyl Coumarins as Selective Inhibitors of Tumor-Associated Carbonic Anhydrase IX and XII: Synthesis, Structure–Activity Relationships, and Molecular Modeling
by Macarena S. Le Pors, Ignacio Aznar, Simone Giovannuzzi, Claudiu T. Supuran, Martin J. Lavecchia and Pedro A. Colinas
Int. J. Mol. Sci. 2026, 27(8), 3659; https://doi.org/10.3390/ijms27083659 - 20 Apr 2026
Viewed by 727
Abstract
Coumarins represent a distinctive class of non-classical carbonic anhydrase inhibitors that interact with the entrance region of the catalytic pocket rather than directly coordinating the catalytic Zn2+ ion. In this study, a series of glycosylated coumarins was synthesized through a copper-catalyzed multicomponent [...] Read more.
Coumarins represent a distinctive class of non-classical carbonic anhydrase inhibitors that interact with the entrance region of the catalytic pocket rather than directly coordinating the catalytic Zn2+ ion. In this study, a series of glycosylated coumarins was synthesized through a copper-catalyzed multicomponent reaction involving propargyl glycosides, salicylaldehyde, and tosyl azide, providing efficient access to iminocoumarin-based glycosides derived from natural carbohydrates. The inhibitory activity of the synthesized compounds was evaluated against human carbonic anhydrase isoforms I, II, IX, and XII using a stopped-flow CO2 hydrase assay. The compounds showed negligible inhibition of the cytosolic isoforms hCA I and hCA II, while displaying moderate activity toward the tumor-associated isoforms hCA IX and hCA XII, with Ki values ranging from 12.9 to 41.8 μM. Among the series, 6-O-(2H-chromene-2-one-3-yl-methyl)-D-galactopyranose (10a) emerged as the most potent inhibitor of hCA IX and XII. Structure–activity relationship analysis indicated that deprotected glycosyl derivatives exhibit improved inhibitory activity compared to protected analogues. To rationalize these observations, molecular docking followed by molecular dynamics simulations and MM-GBSA binding free energy calculations were performed for both anomeric forms of compound 10a. The computational results revealed a clear preference for the β-anomer, particularly in hCA IX and XII, where favorable interactions with catalytic threonine residues and isoform-specific aromatic residues stabilize the ligand within the active-site entrance. These findings provide a molecular explanation for the experimentally observed selectivity and highlight glycosyl coumarins as potential starting points for further optimization toward selective inhibitors of tumor-associated carbonic anhydrases. Full article
(This article belongs to the Special Issue Advances in Glyco-Based Anticancer Agents)
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