Synthesis of 6-aryl-substituted sulfocoumarins and investigation of their carbonic anhydrase inhibitory action

Bioorganic & Medicinal Chemistry
Aiga GrandaneClaudiu T Supuran

Abstract

A series of 6-aryl-substituted 1,2-benzoxathiine 2,2-dioxides was obtained by reacting 6-iodo-sulfocoumarin with arylboronic acids in Suzuki cross-coupling conditions. The new sulfocoumarins incorporating various substituted phenyl moieties in position 6 of the heterocyclic ring were investigated for the inhibition of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms with medicinal chemistry applications, the cytosolic hCA I and II, and the transmembrane, tumor-associated hCA IX and XII. The aryl-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (KIs>10μM) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 9.0 to 95.3nM against hCA IX, and between 3.5 and 14.2nM against hCA XII. As hCA IX and XII are validated anti-tumor targets, such sulfocoumarin, isoform-selective inhibitors may be useful for identifying suitable drug candidates for further clinical trials of this class of pharmacologic agents.

References

Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Dec 8, 2011·Journal of Enzyme Inhibition and Medicinal Chemistry·Ramazan DemirdağClaudiu T Supuran
Apr 4, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Feb 6, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Feb 16, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Fortunato MigliardiniClemente Capasso
Mar 7, 2013·Expert Opinion on Therapeutic Patents·Claudiu T Supuran
Mar 16, 2013·Expert Opinion on Therapeutic Patents·Fabrizio Carta, Claudiu T Supuran
Apr 24, 2013·Expert Opinion on Therapeutic Patents·Andrea ScozzafavaFabrizio Carta
May 1, 2013·Expert Opinion on Drug Discovery·Giuseppina De SimoneClaudiu T Supuran
May 1, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Clemente Capasso, Claudiu T Supuran

❮ Previous
Next ❯

Citations

Nov 3, 2015·Journal of Medicinal Chemistry·Janis LeitansKaspars Tars
Oct 25, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Halise Inci GulClaudiu T Supuran
Oct 27, 2016·Expert Opinion on Drug Discovery·Claudiu T Supuran
Mar 7, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Halise Inci GulClaudiu T Supuran
May 26, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Aleksandrs PustenkoClaudiu T Supuran
Oct 18, 2020·Metabolites·Andrea AngeliClaudiu T Supuran
Feb 23, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran
Apr 25, 2020·Bioorganic & Medicinal Chemistry·Aiga GrandaneClaudiu T Supuran
Jun 8, 2021·Archiv der Pharmazie·Burak KuzuNurettin Menges

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.