Molecular cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Malassezia globosa, a potential antidandruff target

Kirsty S Hewitson; Daniela Vullo; Andrea Scozzafava; Antonio Mastrolorenzo; Claudiu T Supuran

doi:10.1021/jm300203r

Molecular cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Malassezia globosa, a potential antidandruff target

J Med Chem. 2012 Apr 12;55(7):3513-20. doi: 10.1021/jm300203r. Epub 2012 Mar 28.

Authors

Kirsty S Hewitson¹, Daniela Vullo, Andrea Scozzafava, Antonio Mastrolorenzo, Claudiu T Supuran

Affiliation

¹ Union Life Sciences Ltd., 24 Cornhill, London, EC3V 3ND, UK.

PMID: 22424239
DOI: 10.1021/jm300203r

Abstract

A β-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Malassezia globosa has been cloned, characterized, and studied for its inhibition with sulfonamides. This enzyme, designated MG-CA, has significant catalytic activity in the CO(2) hydration reaction and was inhibited by sulfonamides, sulfamates, and sulfamides with K(I) in the nanomolar to micromolar range. Several sulfonamides have also been investigated for the inhibition of growth of M. globosa, M. dermatis, M. pachydermatic, and M. furfur in cultures, whereas a mouse model of dandruff showed that treatment with sulfonamides led to fragmented fungal hyphae, as for the treatment with ketoconazole, a clinically used antifungal agent. These data prompt us to propose MG-CA as a new antidandruff drug target.

MeSH terms

Amino Acid Sequence
Animals
Antifungal Agents / chemistry*
Antifungal Agents / pharmacology
Carbonic Anhydrase Inhibitors / chemistry*
Carbonic Anhydrase Inhibitors / pharmacology
Carbonic Anhydrases / chemistry*
Carbonic Anhydrases / genetics
Cloning, Molecular
Dermatomycoses / drug therapy
Dermatomycoses / microbiology*
Fungal Proteins / antagonists & inhibitors
Fungal Proteins / chemistry*
Fungal Proteins / genetics
Humans
Isoenzymes / antagonists & inhibitors
Isoenzymes / chemistry
Isoenzymes / genetics
Malassezia / drug effects
Malassezia / enzymology*
Mice
Microbial Sensitivity Tests
Models, Molecular
Molecular Sequence Data
Recombinant Fusion Proteins / antagonists & inhibitors
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / genetics
Scalp Dermatoses / drug therapy
Scalp Dermatoses / microbiology*
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology
Sulfonic Acids / chemistry
Sulfonic Acids / pharmacology

Substances

Antifungal Agents
Carbonic Anhydrase Inhibitors
Fungal Proteins
Isoenzymes
Recombinant Fusion Proteins
Sulfonamides
Sulfonic Acids
Carbonic Anhydrases