A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing".

doi:10.1021/JM060967Z

Paper

A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing".

Published Sep 27, 2006 · Brendan L Wilkinson, L. Bornaghi, T. Houston

Journal of medicinal chemistry

Q1 SJR score

162

Citations

2

Influential Citations

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Abstract

Aryl and heteroaryl sulfonamides (ArSO(2)NH(2)) are therapeutically used to inhibit the catalytic activity of carbonic anhydrases (CAs). Using a "click-tail" approach a novel class of glycoconjugate benzene sulfonamides have been synthesized that contain diverse carbohydrate-triazole tails. These compounds were assessed for their ability to inhibit three human CA isozymes in vitro: cytosolic hCA I and hCA II and transmembrane, tumor-associated hCA IX. This isozyme has a minimal expression in normal tissue but is overexpressed in hypoxic tumors and its inhibition is a current approach toward new cancer therapies. The qualitative structure-activity for all derivatives demonstrated that the stereochemical diversity present within the carbohydrate tails effectively interrogated the CA active site topology, to generate several inhibitors that were potent and selective toward hCA IX, an important outcome in the quest for potential cancer therapy applications based on CA inhibition.

In Vitro Study

Highly Cited

Study Snapshot

A novel class of glycoconjugate benzene sulfonamides has been synthesized with diverse carbohydrate-triazole tails, resulting in potent and selective inhibitors of tumor-associated carbonic anhydrase hCA IX, potentially benefiting cancer therapy applications.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

A novel class of carbonic anhydrase inhibitors: glycoconjugate benzene sulfonamides prepared by "click-tailing".

References

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Review Article

Carbonic anhydrase inhibitors show potential as antiglaucoma drugs and can inhibit tumor cell growth, offering potential for developing novel antitumor therapies.

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Recent advances in oligosaccharide synthesis and screening methods may lead to new therapeutic interventions and faster discovery of their biological roles.

Citations

Synthesis of new sulfonamide derivatives: Investigation of their interactions with carbonic anhydrase and cholinesterase enzymes by in vitro and in silico evaluations

Novel sulfonamide derivatives with an aryl sulfonate moiety show low nanomolar inhibition of human carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes, showing potential as new inhibitors.

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Thienopyrimidine derivatives with sulfonamide and other moieties show promising inhibitory activity against various carbonic anhydrase isoforms and show anticancer activity against various cancer cell lines.

Umbelliferone and Its Synthetic Derivatives as Suitable Molecules for the Development of Agents with Biological Activities: A Review of Their Pharmacological and Therapeutic Potential

Umbelliferone and its synthetic derivatives show potential for various therapeutic and diagnostic applications due to their diverse biological activities.

Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold

This study developed a novel library of human carbonic anhydrase inhibitors with potent inhibition properties against tumor-associated isoforms hCA IX and XII, with compounds 1e, 1m, and 1p showing the best selectivity over off-target hCA II.

A simple yet multifaceted 90 years old, evergreen enzyme: Carbonic anhydrase, its inhibition and activation.

Carbonic anhydrase research has advanced over the last three decades, leading to the development of isoform-selective inhibitors/activators, which can be used in obesity management, hypoxic tumors, neurological conditions, and as antiinfectives.