Extending the γ-class carbonic anhydrases inhibition profiles with phenolic compounds

Alessio Nocentini; Sameh M Osman; Sonia Del Prete; Clemente Capasso; Zeid A ALOthman; Claudiu T Supuran

doi:10.1016/j.bioorg.2019.103336

Extending the γ-class carbonic anhydrases inhibition profiles with phenolic compounds

Bioorg Chem. 2019 Dec:93:103336. doi: 10.1016/j.bioorg.2019.103336. Epub 2019 Oct 3.

Authors

Alessio Nocentini¹, Sameh M Osman², Sonia Del Prete³, Clemente Capasso³, Zeid A ALOthman², Claudiu T Supuran⁴

Affiliations

¹ NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Firenze), Italy. Electronic address: alessio.nocentini@unifi.it.
² Chemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
³ Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
⁴ NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Sesto Fiorentino (Firenze), Italy; Chemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: claudiu.supuran@unifi.it.

PMID: 31604186
DOI: 10.1016/j.bioorg.2019.103336

Abstract

γ-Class carbonic anhydrases (CAs; EC 4.2.1.1) lack of extended inhibition characterization in comparison to α- and β-class isozymes. For this reason, a panel of 22 phenols was investigated here for the inhibition of the γ-CAs from the pathogenic bacteria Burkholderia pseudomallei (BpsCAγ), Porphyromonas gingivalis (PgiCA), Vibrio cholerae (VchCAγ) and from the antarctic bacteria Pseudoalteromonas haloplanktis (PhaCAγ) and Colwellia psychrerythraea (CpsCAγ). The exploration of the chemical space around the main phenolic group led to the discovery of a number of such derivatives showing effective, sometimes sub-micromolar inhibition against BpsCAγ (K_Is 0.45-8.6 µM), PgiCA (K_Is 0.36-9.8 µM) and VchCAγ (K_Is 0.47-9.6 µM). A subset of compounds even demonstrated a significant selectivity for the target γ-CAs over the human physiologically most relevant isoform CA II. This study enriches the inhibitory profiles database for γ-class CAs and promotes the identification of new potent and selective inhibitors against bacterial isoforms over human off-target ones. These agents are of remarkable interest and importance in the search of novel, worldwide required, antibiotic agents possessing alternative mechanisms of action as a strategy to overcome the spread to antimicrobic resistance.

Keywords: Antarctic bacteria; Bacteria; Inhibition; Metalloenzyme; Phenol; Resistance; Selectivity; γ-Class.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism
Phenols / pharmacology*
Structure-Activity Relationship
Substrate Specificity

Substances

Carbonic Anhydrase Inhibitors
Phenols
Carbonic Anhydrases