Inhibition of α-, β- and γ-carbonic anhydrases from the pathogenic bacterium Vibrio cholerae with aromatic sulphonamides and clinically licenced drugs - a joint docking/molecular dynamics study

Alessandro Bonardi; Alessio Nocentini; Sameh Mohamed Osman; Fatmah Ali Alasmary; Tahani Mazyad Almutairi; Dalal Saied Abdullah; Paola Gratteri; Claudiu T Supuran

doi:10.1080/14756366.2020.1862102

Inhibition of α-, β- and γ-carbonic anhydrases from the pathogenic bacterium Vibrio cholerae with aromatic sulphonamides and clinically licenced drugs - a joint docking/molecular dynamics study

J Enzyme Inhib Med Chem. 2021 Dec;36(1):469-479. doi: 10.1080/14756366.2020.1862102.

Authors

Alessandro Bonardi^{1

2}, Alessio Nocentini^{1

2}, Sameh Mohamed Osman³, Fatmah Ali Alasmary³, Tahani Mazyad Almutairi³, Dalal Saied Abdullah³, Paola Gratteri^{1

2}, Claudiu T Supuran²

Affiliations

¹ Department NEUROFARBA - Pharmaceutical and Nutraceutical Section; Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Sesto Fiorentino, Italy.
² Department NEUROFARBA - Pharmaceutical and Nutraceutical Section, University of Firenze, Sesto Fiorentino, Italy.
³ Chemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia.

Abstract

The binding mode of aromatic sulphonamides and clinically licenced drugs to the three carbonic anhydrase (CA, EC 4.2.1.1) isoforms from the human pathogen V. cholerae was here thouroghly characterised by a joint docking and molecular dynamics in silico protocol. In fact, VchCA, VchCAβ, and VchCAγ are crucial in the pathogen life cycle and growth and represent innovative targets to fight V. cholerae proliferation overcoming the spreading chemoresistance to the available drugs. A set of 40 sulphonamides/sulfamates VchCAs inhibitors was studied using the proteins homology built 3 D models unveiling the key and stable interactions responsible for a potent CA inhibition. This study has the aim to offer insights and guidelines for the future rational design of potent and selective inhibitors targeting CA isoforms from V. cholerae or other human pathogens.

Keywords: MD; Resistance; inhibition; metalloenzyme; virulence.

MeSH terms

Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / isolation & purification
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Dose-Response Relationship, Drug
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Molecular Docking Simulation*
Molecular Dynamics Simulation*
Molecular Structure
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / isolation & purification
Sulfonamides / pharmacology*
Vibrio cholerae / enzymology*

Substances

Carbonic Anhydrase Inhibitors
Isoenzymes
Sulfonamides
Carbonic Anhydrases

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group No (RG-1441–431).