Natural Polyphenols Selectively Inhibit ß-Carbonic Anhydrase from the Dandruff-Producing Fungus Malassezia globosa: Activity and Modeling Studies.
ChemMedChem
; 13(8): 816-823, 2018 04 23.
Article
en En
| MEDLINE
| ID: mdl-29575699
ABSTRACT
Around 50 % of the worldwide population is affected by dandruff, which is triggered by a variety of factors. The yeast Malassezia globosa has been labeled as the most probable causative agent for the onset of dandruff. The ß-carbonic anhydrase (CA) of MgCA was recently validated as an anti-dandruff target, with its inhibition being responsible for in vivo growth defects in the fungus. As classical CA inhibitors of the sulfonamide type give rise to permeability problems through biological membranes, finding non-sulfonamide alternatives for MgCA inhibition is of considerable interest in the cosmetic field. We recently screened a large library of human (h) CA inhibitors for MgCA inhibition, including different chemotypes, such as monothiocarbamates, dithiocarbamates, phenols, and benzoxaboroles. Herein, we expanded the research toward new MgCA inhibitors by considering a set of natural polyphenols (including flavones, flavonols, flavanones, flavanols, isoflavones, and depsides) that exhibited MgCA inhibitory activity in the micromolar range, as well as selectivity for the fungal isozyme over off-target human isoforms. The binding mode of representative derivatives within the MgCA catalytic cleft was investigated by docking studies using a homology-built model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Anhidrasa Carbónica
/
Polifenoles
/
Caspa
/
Malassezia
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia