Benzoxaboroles: New Potent Inhibitors of the Carbonic Anhydrases of the Pathogenic Bacterium Vibrio cholerae.

ACS Medicinal Chemistry Letters
Alessandro BonardiJean-Yves Winum

Abstract

A series of urea/thiourea substituted benzoxaboroles was investigated for the inhibition of the three carbonic anhydrases encoded by Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). In particular, benzoxaborole derivatives were here first assayed for the inhibition of a γ-class CA, extending the panel of CA classes that benzoxaboroles efficiently target beyond α and β. Inhibition profiles demonstrated that VchCAα was significantly more inhibited compared to VchCAγ and, in turn, more efficiently modulated than VchCAβ. Among the many selective benzoxaborole ligands detected against VchCAα over the off-target hCA II, compound 18, a p-NO2-phenylthiourea derivative, even exhibited a fully selective inhibition profile against the three VchCAs over hCA II. A comprehensive ligand/target interaction study was performed in silico for all three VchCA isoforms providing the first molecular modeling investigation with inhibitors of a γ-class CA to the best of our knowledge. The present study reinforces the rationale behind the use of benzoxaboroles as innovative antibacterial agents with a new mechanism of action, furnishing suggestions for the rational design of new potent and selective inhibitors targeting V. cholerae CAs over human off-targ...Continue Reading

References

Sep 19, 2007·Infection and Immunity·Jyl S MatsonVictor J DiRita
Jul 1, 2009·Infection and Immunity·Basel H Abuaita, Jeffrey H Withey
Jan 17, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Sonia Del PreteClemente Capasso
Nov 19, 2013·Microbial Pathogenesis·Mayra CobaxinJoaquín Sánchez
Sep 4, 2014·Journal of Bacteriology·Joshua J Thomson, Jeffrey H Withey
Dec 3, 2015·Acta Crystallographica. Section D, Biological Crystallography·Marta FerraroniClaudiu T Supuran
Feb 7, 2016·Bioorganic & Medicinal Chemistry·Sonia Del PreteClemente Capasso
Jun 11, 2016·Bioorganic & Medicinal Chemistry·Sonia Del PreteClemente Capasso
Oct 11, 2016·Chemical Communications : Chem Comm·Vincenzo AlterioJean-Yves Winum
Jan 5, 2017·Current Topics in Medicinal Chemistry·Clemente Capasso, Claudiu T Supuran
Mar 18, 2017·Lancet·John D ClemensJan Holmgren
Dec 28, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniJean-Yves Winum
May 5, 2018·Expert Opinion on Therapeutic Patents·Alessio NocentiniJean-Yves Winum
Jul 6, 2018·Expert Opinion on Therapeutic Patents·Claudiu T Supuran, Clemente Capasso
Jul 14, 2018·Nature Reviews. Disease Primers·Craig Baker-AustinJaime Martinez-Urtaza
Jul 27, 2018·Current Opinion in Infectious Diseases·Ana A Weil, Edward T Ryan
Mar 22, 2019·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Wenming WangHongfei Wang
Apr 26, 2019·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Lekshmi NarendrakumarSabu Thomas
Aug 10, 2019·Vaccine·Jacqueline DeenJohn D Clemens
Aug 16, 2019·ACS Medicinal Chemistry Letters·Adèle LarcherMichael Smietana

❮ 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.