Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms

Journal of Enzyme Inhibition and Medicinal Chemistry
Alessio NocentiniClaudiu T Supuran

Abstract

Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a wealth of steroids against four relevant hCA isoforms. Steroids displaying pendants and functional groups of the carboxylate, phenolic or sulfonate types appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9-89.9 µM). Docking studies displayed the different chemotypes CA inhibition mechanisms. Molecular dynamics (MD) gave insights on the stability over time of hyocholic acid binding to CA II.

References

Feb 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D E MilovP W Chun
Apr 1, 1984·Steroids·C Djerassi
Oct 29, 1982·Biochemical and Biophysical Research Communications·I SimonssonS Lindskog
May 6, 2005·Nature·Todd W LaneFrançois M M Morel
Jan 6, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yang TangFrank R Sharp
Nov 23, 2007·Natural Product Reports·James R Hanson
Jan 3, 2008·Nature Reviews. Drug Discovery·Claudiu T Supuran
Jul 8, 2010·Aging Health·Joel V Chua, Wilbur H Chen
Apr 26, 2012·Chemical Communications : Chem Comm·David P Martin, Seth M Cohen
Nov 16, 2012·Natural Product Reports·Jorge A R SalvadorM Luisa Sá e Melo
Jun 11, 2014·Acta Crystallographica. Section D, Biological Crystallography·Christopher D BooneRobert McKenna
Aug 30, 2014·Bioorganic & Medicinal Chemistry Letters·Sonia Del PreteClaudiu T Supuran
Oct 24, 2014·Organic & Biomolecular Chemistry·Serena MostardaAntimo Gioiello
Dec 2, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Jul 9, 2016·Journal of the American College of Cardiology·Desmond J Sheridan, Desmond G Julian
Jul 22, 2016·International Journal of Molecular Sciences·Carrie L LomelinoRobert McKenna
Oct 27, 2016·Expert Opinion on Drug Discovery·Claudiu T Supuran
Dec 6, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anastasia KariotiClaudiu T Supuran
Mar 28, 2017·Bioorganic & Medicinal Chemistry·Yeganeh Entezari HeraviClaudiu T Supuran
Dec 21, 2017·ACS Medicinal Chemistry Letters·Alessio NocentiniClaudiu T Supuran

❮ Previous
Next ❯

Citations

May 6, 2019·International Journal of Molecular Sciences·Amada PashaMaura Calvani
Aug 15, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Mohammad M Al-SaneaClaudiu T Supuran
Aug 23, 2019·Expert Opinion on Drug Discovery·Alessio Nocentini, Claudiu T Supuran
Jan 23, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Rakia Abd AlhameedClaudiu T Supuran
Feb 23, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Aleksandrs PustenkoClaudiu T Supuran
Apr 17, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Aleksandrs PustenkoClaudiu T Supuran
Dec 4, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Aleksandrs PustenkoClaudiu T Supuran
Aug 12, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Claudiu T Supuran
Oct 18, 2020·Metabolites·Andrea AngeliClaudiu T Supuran
Oct 12, 2019·Bioorganic Chemistry·Alessio NocentiniClaudiu T Supuran
May 22, 2020·ACS Medicinal Chemistry Letters·Wagdy M EldehnaClaudiu T Supuran
Feb 23, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran
Sep 16, 2020·International Journal of Biological Macromolecules·Belgin SeverŞükrü Beydemir
May 4, 2021·Digestive Diseases and Sciences·Minna NortunenTuomo J Karttunen
Jun 8, 2021·Archiv der Pharmazie·Burak KuzuNurettin Menges
Dec 10, 2021·Chemistry : a European Journal·Davide SbravatiClaudiu T Supuran

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

Simulation Interaction Diagram
Macromodel
Maestro
Cheminformatics –
– Schrödinger suite
PRISM

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.