Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions

Sonia Del Prete; Andrea Angeli; Cynthia Ghobril; Julien Hitce; Cécile Clavaud; Xavier Marat; Claudiu T Supuran; Clemente Capasso

doi:10.3390/metabo10010039

Sulfonamide Inhibition Profile of the β-Carbonic Anhydrase from Malassezia restricta, An Opportunistic Pathogen Triggering Scalp Conditions

Metabolites. 2020 Jan 16;10(1):39. doi: 10.3390/metabo10010039.

Authors

Sonia Del Prete¹, Andrea Angeli², Cynthia Ghobril³, Julien Hitce³, Cécile Clavaud³, Xavier Marat³, Claudiu T Supuran², Clemente Capasso¹

Affiliations

¹ Institute of Biosciences and Bioresources, CNR, Via Pietro Castellino 111, 80131 Napoli, Italy.
² Section of Pharmaceutical and Nutraceutical Sciences, Department of Neurofarb, University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
³ L'Oréal Research and Innovation, 93601 Aulnay-sous-Bois, France.

Abstract

The critical CO₂ hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO₂ and HCO₃^- at the cellular level, which will not be ensured by the low velocity of the uncatalyzed reaction. CA inhibition may impair the growth of microorganisms. In the yeasts, Candida albicans and Malassezia globosa, the activity of the unique β-CA identified in their genomes was demonstrated to be essential for growth of the pathogen. Here, we decided to investigate the sulfonamide inhibition profile of the homologous β-CA (MreCA) identified in the genome of Malassezia restricta, an opportunistic pathogen triggering dandruff and seborrheic dermatitis. Among 40 investigated derivatives, the best MreCA sulfonamide inhibitors were dorzolamide, brinzolamide, indisulam, valdecoxib, sulthiam, and acetazolamide (K_I < 1.0 μM). The MreCA inhibition profile was different from those of the homologous enzyme from Malassezia globosa (MgCA) and the human isoenzymes (hCA I and hCA II). These results might be useful to for designing CA inhibitor scaffolds that may selectively inhibit the dandruff-producing fungi.

Keywords: CA inhibitors; Malassezia globosa; Malassezia restricta; carbonic anhydrases; dandruff; metalloenzymes; seborrheic dermatitis; sulfonamides.